Table 1 Summary of the 33 variants detected in 22 genes in 14 cases of otherwise unexplained intrauterine fetal demise.
From: Cardio-pathogenic variants in unexplained intrauterine fetal death: a retrospective pilot study
Gene | Gene description | Primary dysfunction | Location | Nucleotide change | Amino acid change | Effect | RefSeq | ACMG classification | ACMG criteria | VarSome in silico prediction |
|---|---|---|---|---|---|---|---|---|---|---|
AKAP9 | A-Kinase Anchoring Protein 9 | Arrhythmogenic | 7q21-q22 | c.763A > C | p.Thr255Pro | Missense | NM_005751.4 | VUS | PM2 | 12 benign, 8 damaging |
ANK2 | Ankyrin 2 | Arrhythmogenic | 4q25-q27 | c.7436A > G | p.Lys2479Arg | Missense | NM_001148.4 | VUS | 12 benign, 7 damaging | |
c.11459G > A | p.Arg3820Gln | Missense | NM_001148.4 | Likely benign | BS1, BP6, BP4 | 17 benign, 3 damaging | ||||
c.9520A > G | p.Thr3174Ala | missense | NM_001148.4 | VUS | PM2, BP4 | 19 benign, 1 damaging | ||||
DSG2 | Desmoglein 2 | Cardiac morphology, arryhthmogenic | 18q12.1 | c.3205A > G | p.Met1069Val | missense | NM_001943.3 | VUS | PM2, BP4 | 20 benign, 0 damaging |
c.880A > G | p.Lys294Glu | missense | NM_001943.3 | VUS | 11 damaging, 9 benign | |||||
DSP | Desmoplakin | Cardiac morphology | 6p24 | c.5513G > A | p.Arg1838His | missense | NM_004415.2 | VUS | BP1 | 10 damaging, 10 benign |
ILK | Integrin-linked kinase | Cardiac morphology | 11p15.5-p15.4 | c.521G > A | p.Arg174His | missense | NM_004517.2 | VUS | 8 benign, 7 damaging | |
c.684 T > G | p.Ser228Arg | missense | NM_004517.2 | VUS | PM2 | 12 benign, 8 damaging | ||||
JPH2 | Junctophilin 2 | Cardiac morphology | 20q13.12 | c.572C > G | p.Pro191Arg | missense | NM_020433.4 | Likely benign | BS1, BP4 | 18 benign, 2 damaging |
KCNE1 | Potassium voltage-gated channel subfamily E member 1 | Arrhythmogenic | 21q22.12 | c.200G > A | p.Arg67His | missense | NM_001270402.1 NM_000219.6 (HGMD; ClinVar) | VUS | PM2, PM5, PP3 | 12 damaging, 3 benign |
LAMA2 | Laminin alpha 2 (merosin) | Cardiac morphology | 6q22-q23 | c.6598C > T | p.Arg2200Cys | missense | NM_000426.3 | VUS | PP3, BP1 | 17 damaging, 2 benign |
c.3778G > A | p.Glu1260Lys | missense | NM_000426.3 | VUS | PM2, BP1 | 12 damaging, 7 benign | ||||
MYH7 | Myosin heavy polypeptide 7 | Cardiac morphology | 14q12 | c.3200 T > C | p.Met1067Thr | missense | NM_000257.2 | VUS | PM2, PP2, PP3 | 17 damaging, 3 benign |
c.2224G > A | p.Ala742Thr | missense | NM_000257.2 | VUS/Likely pathogenic | PM1, PM2, PP2, BP4 | 14 benign, 5 damaging | ||||
MYO6 | Myosin VI | Cardiac morphology | 6q13 | c.2307C > G | p.Ile769Met | missense | NM_004999.3 | VUS | PM2, BP4 | 15 benign, 6 damaging |
MYOM1 | Myomesin 1 | Cardiac morphology | 18p11.31 | c.4814C > T | p.Ser1605Leu | missense | NM_003803.3 | VUS | 11 benign, 9 damaging | |
c.5045dupA | p.Lys1683GlufsTer16 | Duplication (frameshift) | NM_003803.3 | Likely benign | BS1, BP6 | – | ||||
MYPN | Myopalladin | Cardiac morphology | 10q21.3 | c.3589G > A | p.Gly1197Ser | missense | NM_001256267.1 NM_032578.3 (HGMD) | VUS | PM2, PP3 | 18 damaging, 3 benign |
NDUFV2 | NADH dehydrogenase (ubiquinone) flavoprotein 2 | Cardiac morphology | 18p11.31-p11.2 | c.604G > A | p.Glu202Lys | missense | NM_021074.4 | VUS | BP4 | 14 benign, 6 damaging |
NEBL | Nebulette | Cardiac morphology | 10p12 | c.267C > G | p.Tyr89Ter | stop | NM_006393.2 | VUS/Likely benign | BS1 | - |
OBSCN | Obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF | Cardiac morphology | 1q42.13 | c.23631A > T | p.Arg7877Ser | missense | NM_001098623.1 (obscntv2 in HGMD) NM_001271223.2 (ClinVar) NM_052843.3 (OBSCN in HGMD) | VUS | PM2, BP4 | 17 benign, 3 damaging |
c.4393G > A | p.Glu1465Lys | missense | NM_001098623.1 | VUS | BS1, BP4 | 14 benign, 6 damaging | ||||
c.7457 T > C | p.Val2486Ala | missense | NM_001098623.1 | VUS | 13 benign, 8 damaging | |||||
c.9545C > T | p.Ala3182Val | missense | NM_001098623.1 | VUS | BP4 | 15 benign, 6 damaging | ||||
PRKAG2 | Protein Kinase AMP-Activated Non-Catalytic Subunit Gamma 2 | Cardiac morphology | 7q36.1 | c.1475 T > A | p.Ile492Asn | missense | NM_016203.3 | VUS | PP2, PP3 | 18 damaging, 2 benign |
RBM20 | RNA binding motif protein 20 | Cardiac morphology | 10q25.2 | c.1451C > T | p.Thr484Ile | missense | NM_001134363.1 | Likely benign | BS1, BP4, PP2 | 13 benign, 3 damaging |
SCN10A | Sodium voltage-gated channel alpha subunit 10 | Arrhythmogenic | 3p22.2 | c.3674 T > C | p.Ile1225Thr | missense | NM_006514.2 | Likely benign | PP3, BS1, BS2 | 18 damaging, 2 benign |
SCNN1A | Sodium Channel Epithelial 1 Subunit Alpha | Arrhythmogenic | 12p13 | c.752G > C | p.Arg251Thr | missense | NM_001159576.1 NM_001038.5 (HGMD, ClinVar) | VUS | BP4, PM2 | 21 benign, 0 damaging |
c.1618G > A | p.Val540Met | Missense | NM_001159576.1 | VUS | BP4, PS3 | 15 benign, 4 damaging | ||||
TBX5 | T-Box Transcription Factor 5 | Cardiac morphology, arryhthmogenic | 12q24.1 | c.1115C > T | p.Ser372Leu | Missense | NM_181486.2 NM_000192.3 (HGMD) | VUS | BS1, PS3, PP5 | 11 benign, 8 damaging |
TNNT2 | Troponin T2 | Cardiac morphology | 1q32 | c.83C > T | p.Ala28Val | Missense | NM_001001430.2 NM_001276345.2 NM_000364.3 (ClinVar) | VUS | BS1, PP2, BP4 | 16 benign, 4 damaging |
TRPM4 | Transient receptor potential cation channel subfamily M member 4 | Arrhythmogenic | 19q13.33 | c.1871 T > C | p.Val624Ala | Missense | NM_017636.3 | VUS | PM2, BP4 | 18 benign, 3 damaging |
