ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5263G>T (p.Ala1755Ser)

dbSNP: rs730880814
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158690 SCV000208625 uncertain significance not provided 2017-05-23 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH7 gene. The A1755S variant has not been published as pathogenic or been reported as benign to our knowledge. The A1755S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, the A1755S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Furthermore, the majority of in silico analyses predict this variant is probably damaging to the protein structure/function. Nevertheless, this variant lacks this variant lacks sufficient evidence, such as segregation studies, functional studies, and clinical data to support its pathogenicity.
Invitae RCV000803340 SCV000943205 uncertain significance Hypertrophic cardiomyopathy 2023-05-09 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 181276). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1755 of the MYH7 protein (p.Ala1755Ser).

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