ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.316A>G (p.Met106Val)

dbSNP: rs773526113
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001018942 SCV001180240 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-23 criteria provided, single submitter clinical testing The p.M106V variant (also known as c.316A>G), located in coding exon 2 of the SMARCA4 gene, results from an A to G substitution at nucleotide position 316. The methionine at codon 106 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Missense and in-frame variants in SMARCA4 are known to cause neurodevelopmental disorders; however, such associations with rhabdoid tumor predisposition syndrome including small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Jelinic P et al. Nat Genet. 2014 May;46(5):424-6). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001236959 SCV001409702 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-10-09 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 106 of the SMARCA4 protein (p.Met106Val). This variant is present in population databases (rs773526113, gnomAD 0.0009%). 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: 823059). 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.
Genome-Nilou Lab RCV001809920 SCV002056293 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing
GeneDx RCV003442148 SCV004170374 uncertain significance not provided 2023-10-18 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
Baylor Genetics RCV001236959 SCV004204883 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-10-16 criteria provided, single submitter clinical testing

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