ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4238C>T (p.Ser1413Leu)

gnomAD frequency: 0.00001  dbSNP: rs730880796
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158645 SCV000208580 likely pathogenic not provided 2013-01-16 criteria provided, single submitter clinical testing p.Ser1413Leu (S1413L) TCG>TTG: c.4238 C>T in exon 31 of the MYH7 gene (NM_000257.2). The Ser1413Leu variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ser1413Leu results in a non-conservative amino acid substitution of a polar Serine with a non-polar Leucine at a position that is conserved across species. In silico analysis predicts Ser1413Leu is damaging to the protein structure/function. Mutations in nearby codons (Leu1414Met, Arg1420Gln, Arg1420Trp) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. Furthermore, the Ser1413Leu variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, while Ser1413Leu is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in DCM panel(s).
Invitae RCV001214464 SCV001386147 uncertain significance Hypertrophic cardiomyopathy 2023-07-10 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 181250). 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 expected to disrupt MYH7 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. This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1413 of the MYH7 protein (p.Ser1413Leu). This variant is present in population databases (rs730880796, gnomAD 0.004%).

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