ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.2240C>T (p.Ala747Val)

gnomAD frequency: 0.00001  dbSNP: rs2088720436
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001206315 SCV001377617 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-09-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 747 of the SMARCA4 protein (p.Ala747Val). 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: 937329). 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. 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 RCV002418685 SCV002725477 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-15 criteria provided, single submitter clinical testing The p.A747V variant (also known as c.2240C>T), located in coding exon 14 of the SMARCA4 gene, results from a C to T substitution at nucleotide position 2240. The alanine at codon 747 is replaced by valine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003442767 SCV004169238 uncertain significance not provided 2023-04-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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

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