ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1373T>C (p.Ile458Thr)

gnomAD frequency: 0.00001  dbSNP: rs774807696
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497477 SCV000590287 uncertain significance not provided 2024-08-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; 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
Labcorp Genetics (formerly Invitae), Labcorp RCV000647071 SCV000768858 uncertain significance Hypertrophic cardiomyopathy 14 2024-12-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 458 of the MYH6 protein (p.Ile458Thr). This variant is present in population databases (rs774807696, gnomAD 0.006%). 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: 432548). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV002383957 SCV002696384 uncertain significance Cardiovascular phenotype 2024-03-27 criteria provided, single submitter clinical testing The p.I458T variant (also known as c.1373T>C), located in coding exon 11 of the MYH6 gene, results from a T to C substitution at nucleotide position 1373. The isoleucine at codon 458 is replaced by threonine, an amino acid with similar 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.
Fulgent Genetics, Fulgent Genetics RCV002489218 SCV002797747 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-08-15 criteria provided, single submitter clinical testing

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