Infertility & Pregnancy Loss Panel — Physician Summary
Pre-conception screen · infertility & pregnancy-loss genes · both partners
- Patients
- Maya & Daniel
- Reason for testing
- 3 recurrent first-trimester losses
- Sample type
- Saliva (both partners)
- Report date
- 2026-07-14
- Test performed
- Pre-conception genetic review · one or both partners
- Genome build
- GRCh38
- Panel version
- Fertility & Loss Panel · v1 (demo)
- Reviewed by
- Christina, Genetic Counselor
RESULT: POSITIVE2 reportable findings — 1 higher-risk, 1 carrier
This panel evaluated 750+ genes associated with infertility, embryo viability, and pregnancy loss in both reproductive partners. Reportable findings are listed below; no other clinically significant variants were identified in the remaining genes evaluated. Findings are screening results, not diagnoses.
Egg source
Maya
POSITIVE — 2 reportable findings (1 higher risk, 1 carrier)
One higher-risk reproductive variant, one carrier variant
Sperm source
Daniel
NEGATIVE — no reportable variants
No reduced-viability variants identified
Results summary — partners side by side
One row per variant found in either partner. The shaded pair of columns gives each partner's result for that same variant — read across.
| Result by partner — same variant, one column each | ||||
|---|---|---|---|---|
| Gene · variant | MayaEgg source | DanielSperm source | Inheritance | Couple implication |
| TUBB8TUBB8 c.686T>C (p.Val229Ala) | Higher riskPathogenic | NegativeNot applicable — maternal-effect gene acts in the egg | Maternal-effect (oocyte) | Acts through the egg source's own genotype; the sperm source's result does not change the risk. |
| DHCR7DHCR7 c.964-1G>C · one copy | CarrierPathogenic · heterozygous | Negative | Autosomal recessive · heterozygous | One carrier; Daniel negative — no increased risk for this pairing (residual risk only). |
| All other panel genes750+ genes screened in every group | Negative | Negative | — | No other reportable variants in any panel category. |
Clinical summary
HIGHER RISK — TUBB8 · oocyte maturation / early embryonic arrest
A single pathogenic variant, c.686T>C (p.Val229Ala), was identified in TUBB8 in the egg source. TUBB8 encodes the β-tubulin isotype of the oocyte meiotic spindle; pathogenic variants are associated with oocyte maturation arrest, fertilization failure, and pre-implantation embryonic arrest (Feng 2016; Zheng 2021). In the context of three chromosomally untested first-trimester losses, this finding offers a plausible mechanism.
Evidence & predictive value: gene–disease validity is established (ESHRE FeRGI definitive, score 17 of 18). Penetrance is variable and per-cycle positive predictive value is not yet established — a finding does not predict that every egg or embryo is affected.
CARRIER — DHCR7 · Smith-Lemli-Opitz syndrome
A single pathogenic variant, c.964-1G>C, was identified in DHCR7 in the egg source (heterozygous). Biallelic DHCR7 variants cause Smith-Lemli-Opitz syndrome (autosomal recessive). The sperm source tested negative for DHCR7 variants; a negative screen reduces but does not eliminate carrier risk (residual risk). No partner action is indicated for the current pairing.
Recommendations
- Confirmatory testing of the TUBB8 variant in a CLIA-certified laboratory if results will direct management.
- IVF with preimplantation genetic testing (PGT-A, with single-variant screening for the familial TUBB8 variant) may be discussed as a strategy to reduce further losses.
- No action indicated for the DHCR7 carrier result with the current partner; relevant to cascade or future-partner testing only.
- Genetic counseling is included with this report: patients may schedule directly at cal.com/team/reticular-bio, and the counselor is available to the clinical team for case review.
Panel scope & method
Sequencing-based screen of 750+ genes across both partners, grouped by reproductive mechanism: genes that help the egg mature and divide (18), genes for fertilization (10), genes that run the embryo's first days (12), genes tied to molar pregnancy (5), genes for ovarian reserve & egg supply (43), genes for the hormones that drive ovulation (26), genes a pregnancy needs to keep growing (182), genes a newborn needs to thrive (377), blood-clotting & pregnancy-support genes (12), genes for sperm (34). Survival genes are the Human Intolerome's “Known” evidence tier (RPLdb), split by the database's recorded timing of lethality; infertility groups take ESHRE FeRGI genes with moderate-or-stronger gene–disease evidence (score ≥9 of 18). Variant classification (ACMG) is reported separately from the strength of reproductive evidence.
Limitations
- Screening, not diagnostic, testing: results identify reproductive risk factors and carrier states; they do not diagnose any condition in the individuals tested or predict the outcome of any specific pregnancy.
- This change acts on the egg, not the baby. TUBB8 works in the egg and earliest embryo, not in a growing baby.
- A carrier copy doesn't cause loss. One copy of a recessive gene like DHCR7 doesn't cause pregnancy loss — a condition needs a damaged copy from both parents.
- It tests parents, not a pregnancy. This is a pre-conception panel — not a prenatal or newborn test.
References
- RPLdb — The Human Intolerome database (full survival-gene list)
- ESHRE FeRGI — Female Reproductive Genetics gene database
- Aminbeidokhti et al. — Recurrent euploid pregnancy loss (medRxiv 2025)
- Yatsenko et al. — The Human Intolerome (Genet Med 2026)
- Chen et al. — Genetic landscape of human oocyte/embryo defects (Cell Genomics 2025)
- Sang, Ray & Wang — Understanding the genetics of human infertility (Science 2023)
- Zheng et al. — TUBB8 variant & phenotype spectrum (J Assist Reprod Genet 2021)
- Slim et al. — NLRP7 in recurrent hydatidiform mole (Hum Mutat 2022)
- Maksiutenko et al. — PLoV pregnancy-loss variant database (Database 2025)
Appendix — genes evaluated (full panel list)
Genes that help the egg mature and divide (18)
TUBB8, PATL2, TRIP13, TACC3, CDC20, KIF11, TUBA4A, KIF18A, HAUS6, LHX8, TBPL2, ZFP36L2, PABPC1L, MLH3, KASH5, LHCGR, SYCP3, CCNB3
Genes for fertilization (10)
ZP1, WEE2, PLCZ1, ZP2, ZP3, ZP4, ASTL, ACTL7A, ACTL9, IZUMO1R
Genes that run the embryo's first days (12)
PADI6, TLE6, NLRP5, NLRP2, BTG4, CHEK1, OOEP, KPNA7, MOS, FBXO43, MEI4, PANX1
Genes tied to molar pregnancy (5)
NLRP7, KHDC3L, MEI1, TOP6BL, REC114
Genes for ovarian reserve & egg supply (43)
AARS2, AIRE, BMP15, BNC1, CLPP, DCAF17, EIF2B2, EIF2B5, EIF4ENIF1, ERCC6, FANCA, FANCM, FIGLA, FMR1, FOXL2, FOXO3A, FSHR, GALT, GDF9, GGPS1, HARS2, HFM1, HSD17B4, LARS2, MCM8, MCM9, MSH4, MSH5, NOBOX, NR5A1, NUP107, PMM2, POF1B, POR, PSMC3IP, REC8, SETX, SLC29A3, SOHLH1, STAG3, SYCE1, TRIM37, TWNK
Genes for the hormones that drive ovulation (26)
AMH, CHD7, FGF8, FGFR1, FSHB, GNRH1, GNRHR, HJV, INSR, KAL1, KISS1R, LEP, LEPR, LMNA, PNPLA6, POLR3A, PROK2, PROKR2, PROP1, RNF216, SOX10, SOX2, STUB1, TAC3, TACR3, TUBB3
Genes a pregnancy needs to keep growing (182)
AAAS, ABCB4, ABCC6, ACO2, ACTA1, ACTG2, ADAMTS2, ADGRG6, ADSL, AGK, AGT, AGTR1, AK2, AKT2, ALDH18A1, ALG1, ALG8, ALG9, AMACR, AMT, ANK2, ANOS1, ANTXR2, ARHGAP31, ARID1B, ASCC1, ASNS, ASXL1, ATP6V1E1, ATP7A, B3GAT3, B4GAT1, BCKDHB, BCOR, BLTP1, BMPR2, BUB1B, C1QBP, CCBE1, CEP290, CHRND, CHRNE, CILK1, COG7, COL11A1, COL1A1, COL1A2, COX15, CRB2, CSPP1, CTSA, CYP26B1, CYP27A1, DLD, DNAH5, DNM2, DPAGT1, DYNC2H1, DYNC2LI1, EBP, ENG, ETFDH, EVC2, EXTL3, F10, F7, FAM111A, FANCL, FBN2, FLNA, FRAS1, G6PC1, GATA4, GLDN, GLE1, GLI2, GLI3, GLUL, GNAS, GNPAT, GNPTAB, GPC3, GPI, GPX4, GRIP1, GUCY2D, HADHA, HADHB, HBB, HCCS, HNF1B, HRAS, HSD17B10, HSPD1, HYLS1, IFT122, IFT80, IKBKG, ITGA8, ITGB4, JAM3, KCNH2, KCNJ2, KIAA1109 (BLTP1), KIF7, KMT2D, L1CAM, LONP1, MAGED2, MAGEL2, MECOM, MECP2, MED12, MIPEP, MKS1, MTOR, MYBPC3, MYH7, NAA10, NDUFAF5, NDUFB11, NDUFV1, NEK1, NEK8, NEU1, NPC2, NPHP3, NPHS1, NSDHL, OBSCN, OFD1, OTX2, P3H1, PHGDH, PIEZO1, PIGA, PIGW, PITX1, PLD1, POMGNT1, PORCN, PPIB, PRRX1, PTH1R, PTPN11, RAG1, RBM10, RET, RFT1, RIPK4, RIT1, RLIM, RMND1, SBDS, SCN5A, SCO2, SLC26A2, SOX18, SOX9, SPINK5, TAZ, TBX1, TBX19, TCTN2, THSD1, TMEM126B, TMEM231, TMEM67, TRIP11, TRPV4, TSEN54, TSPYL1, TTC37, TTC7A, TTN, TUFM, UBR1, WASHC5, WDR35, WDR73, WNT7A, WWOX
Genes a newborn needs to thrive (377)
ABAT, ABCA3, ACADM, ACE, ADAMTSL2, AIMP1, AKR1D1, ALDH1A3, ALDH7A1, ALPL, AMER1, ANK1, AP1S1, AP4M1, ARG1, ARHGDIA, ARV1, ARX, ASAH1, ASPA, ASS1, ATP6V1B1, ATP6V1B2, ATRX, B3GALT6, BCKDHA, BMPER, BOLA3, BRAT1, CANT1, CARD11, CASK, CCDC115, CD3D, CD3E, CD3G, CD40LG, CD96, CDKN1C, CDSN, CHAT, CHST14, CIT, CLCN7, CLMP, CLPB, COA6, COA8, COG6, COL2A1, COL3A1, COLEC10, COQ2, COQ9, COX10, CPOX, CPS1, CRLF1, CRPPA, CRTAP, CRYAB, CSF3R, CXCR4, CYP11B1, CYP11B2, CYP7B1, D2HGDH, DAG1, DBT, DDR2, DGUOK, DHCR7, DHDDS, DHFR, DIS3L2, DKC1, DLL3, DNAI1, DNAJC19, DNM1L, DOLK, DPM2, DPYD, DYNC2I1, DYNC2I2, EARS2, ECEL1, EDA, EDN3, EDNRB, EFEMP2, EIF2AK3, ELAC2, ELOVL4, EMG1, ENPP1, EPB41, EPCAM, EPG5, ERBB3, ERCC1, ESCO2, ETFB, ETHE1, EXOSC3, EXOSC8, EYA1, FANCB, FARS2, FBLN5, FBN1, FBP1, FBXL4, FCN3, FERMT3, FGFR3, FH, FHL1, FIG4, FKRP, FLAD1, FOXF1, FOXP3, FOXRED1, GALC, GATA6, GBA1, GBE1, GCSH, GFAP, GGCX, GLDC, GLIS3, GNAO1, GRIN1, GTPBP3, GUCY2C, GYS1, HAAO, HADH, HAX1, HELLS, HIBCH, HSPG2, IER3IP1, IFT43, IFT81, IGHMBP2, IL2RG, ISCA2, ITCH, ITGA3, ITGA6, ITPA, IVD, KCNA1, KCNJ10, KCNJ5, KCNT1, KDSR, KIF5A, KLHL41, KRT1, KRT10, KYNU, LAGE3, LAMA3, LAMC2, LARGE1, LBR, LGI4, LIAS, LIFR, LIPA, LIPT1, LIPT2, LMBRD1, LRPPRC, MANBA, MAPRE2, MBTPS2, MCCC2, MDH2, MESP2, MKKS, MLYCD, MMUT, MOCS1, MOCS2, MPC1, MPDU1, MPI, MPV17, MRPS22, MRPS34, MTM1, MTO1, MUSK, MYLK2, MYO18B, MYO5B, NAGA, NAGS, NAXE, NDUFA1, NDUFA11, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFB3, NDUFS1, NDUFS2, NDUFS4, NDUFS6, NEB, NEK9, NNT, NOTCH2, NR1H4, NTRK1, NUP62, OCLN, ORAI1, OSGEP, OSTM1, OTC, OTULIN, OXCT1, PAM16, PAX6, PC, PCCA, PCCB, PDGFRB, PDHB, PDHX, PDP1, PDSS2, PEPD, PET100, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX3, PEX5, PEX6, PEX7, PFKM, PHF8, PIGO, PIGV, PIGY, PIP5K1C, PKD1L1, PKD2, PKHD1, PKLR, PLA2G6, PLEC, PLPBP, PNPO, POLA1, POMC, POMGNT2, POMT2, POU1F1, PRPS1, PSAP, PTF1A, PUF60, PYGM, RAB27A, RAD51C, RAG2, RARS2, RBM8A, RFX6, RPSA, RRM2B, RTTN, RXYLT1, RYR1, SALL1, SAMHD1, SCN2A, SCN4A, SCNN1B, SCNN1G, SCO1, SDHA, SDHAF1, SDHD, SETBP1, SFTPA2, SFTPB, SGPL1, SH3PXD2B, SIK1, SIX3, SLC16A2, SLC19A3, SLC25A1, SLC25A19, SLC25A20, SLC25A22, SLC25A24, SLC25A26, SLC25A4, SLC25A46, SLC35D1, SLC39A14, SLC46A1, SLC52A3, SLC5A7, SLC6A9, SMARCAL1, SMARCD2, SMCHD1, SMG9, SMN1, SNRPB, SOX3, SPECC1L, SPEG, SPINT2, STAMBP, STAR, STAT1, STAT2, STIM1, STRA6, SUCLG1, SUMF1, SUOX, TBC1D24, TBCE, TBX20, TCIRG1, TCN2, TFAP2A, TFAP2B, TGDS, TIMMDC1, TINF2, TJP2, TK2, TMEM165, TMEM70, TOE1, TP53RK, TP63, TPI1, TPM3, TPRKB, TRAIP, TREX1, TRMT10C, TRMU, UBA1, UFM1, VDR, VKORC1, VMA21, VPS33B, VPS45, WARS2, XIAP, YARS2, ZIC2, ZIC3, ZMPSTE24, ZNF148
Blood-clotting & pregnancy-support genes (12)
F5, F2, SERPINC1, PROC, PROS1, ANXA5, NOS3, SERPINE1, F13A1, THBD, FGA, FLT1
Genes for sperm (34)
CFTR, AURKC, DPY19L2, DNAH1, TEX11, ADGRG2, SUN5, PMFBP1, CATSPER1, CATSPER2, USP26, STAG3, SYCE1, MEIOB, MSH4, SPATA22, PNLDC1, PIWIL1, CFAP43, CFAP44, TTC29, CEP135, TEX14, TEX15, SYCP2, M1AP, ZMYND15, DNAH17, CFAP65, ARMC2, QRICH2, TTC21A, SPEF2, DNAH8
Gene lists follow published evidence tiers: the pregnancy and newborn groups hold the “Known”-evidence genes of the 934-entry Human Intolerome, split by the database's own record of when a fault is lethal (emerging and candidate research genes are screened but not listed individually), and the infertility groups list every ESHRE FeRGI gene with moderate-or-stronger gene–disease evidence (score 9–18 of 18). Each gene is listed once in its best-fitting group — except MSH4, STAG3, and SYCE1, which appear under both ovarian reserve and sperm because they act in meiosis in both sexes. The 750+ total is cross-referenced against other laboratories' infertility panels.