ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.4602G>C (p.Gln1534His)

dbSNP: rs757889804
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001022913 SCV001184708 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-21 criteria provided, single submitter clinical testing The p.Q1566H variant (also known as c.4698G>C), located in coding exon 32 of the SMARCA4 gene, results from a G to C substitution at nucleotide position 4698. The glutamine at codon 1566 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001862239 SCV002307704 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1566 of the SMARCA4 protein (p.Gln1566His). This variant is present in population databases (rs757889804, gnomAD 0.003%). 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: 825106). 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.

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