Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000548438 | SCV000648107 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1452 of the SMARCA4 protein (p.Gly1452Ala). 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. ClinVar contains an entry for this variant (Variation ID: 470397). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SMARCA4 protein function. 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 | RCV001022346 | SCV001184071 | likely benign | Hereditary cancer-predisposing syndrome | 2021-05-05 | 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. |
| Genome- |
RCV001809529 | SCV002056917 | uncertain significance | Intellectual disability, autosomal dominant 16 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV001809529 | SCV004171345 | uncertain significance | Intellectual disability, autosomal dominant 16 | criteria provided, single submitter | clinical testing | The missense c.4259G>C (p.Gly1420Ala) variant in SMARCA4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gly1420Ala variant is novel (not in any individuals) in both gnomAD Exomes and 1000 Genomes databases. This variant has been reported to the ClinVar database as Likely Benign / Uncertain Significance. The amino acid change p.Gly1420Ala in SMARCA4 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 1420 is changed to a Ala changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant Uncertain Significance (VUS). |