Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001967504 | SCV002212559 | uncertain significance | Atrioventricular septal defect 4 | 2022-06-27 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is also known as c.962G>A (p.Arg321Gln). This missense change has been observed in individual(s) with clinical features of GATA4-related conditions (PMID: 30293987, 32901917). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 320 of the GATA4 protein (p.Arg320Gln). |
| 3billion | RCV003314025 | SCV004013822 | likely pathogenic | Testicular anomalies with or without congenital heart disease | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.85; 3Cnet: 0.88). Same nucleotide change resulting in same amino acid change (PMID: 30293987 / 3billion dataset) and a different missense change at the same codon (p.Arg321Trp / ClinVar ID: VCV000545667 / PMID: 20854389) have been previously reported to be associated with GATA4 -related disorder. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |