ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4352T>C (p.Phe1451Ser)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002332282 SCV002627921 uncertain significance Cardiovascular phenotype 2021-12-29 criteria provided, single submitter clinical testing The p.F1451S variant (also known as c.4352T>C), located in coding exon 28 of the MYH6 gene, results from a T to C substitution at nucleotide position 4352. The phenylalanine at codon 1451 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003317595 SCV004021555 uncertain significance not provided 2023-07-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV005058367 SCV005724478 uncertain significance Hypertrophic cardiomyopathy 14 2024-05-09 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1451 of the MYH6 protein (p.Phe1451Ser). This variant is present in population databases (rs764920377, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1739945). 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 MYH6 protein function with a positive predictive value of 80%. 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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