Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001883131 | SCV002141161 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2021-11-29 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 565 of the SMARCA4 protein (p.Thr565Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV002397816 | SCV002712731 | likely benign | Hereditary cancer-predisposing syndrome | 2024-11-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Victorian Clinical Genetics Services, |
RCV002471174 | SCV002768441 | uncertain significance | Intellectual disability, autosomal dominant 16 | 2020-05-21 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_001128849.1(SMARCA4):c.1693A>G in exon 10 of 36 of the SMARCA4 gene. This substitution is predicted to create a minor amino acid change from a threonine to an alanine at position 565 of the protein, NP_001122321.1(SMARCA4):p.(Thr565Ala). The threonine at this position has very high conservation (100 vertebrates, UCSC) and is not situated in a known domain. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database and has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VUS. Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |