ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.1787C>T (p.Thr596Met)

gnomAD frequency: 0.00001  dbSNP: rs779952581
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528836 SCV000647965 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 596 of the SMARCA4 protein (p.Thr596Met). This variant is present in population databases (rs779952581, gnomAD 0.01%). 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: 470259). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SMARCA4 protein function with a negative predictive value of 95%. 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 RCV000575000 SCV000672110 benign Hereditary cancer-predisposing syndrome 2024-05-15 criteria provided, single submitter clinical testing This alteration is classified as 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-Nilou Lab RCV001809489 SCV002056454 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003424125 SCV004139555 uncertain significance not provided 2023-09-01 criteria provided, single submitter clinical testing SMARCA4: PP2, BP4
GeneDx RCV003424125 SCV004168782 uncertain significance not provided 2023-04-10 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32686686)

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