ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.167G>C (p.Gly56Ala)

dbSNP: rs727504870
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156232 SCV000205948 uncertain significance not specified 2013-11-26 criteria provided, single submitter clinical testing The Gly56Ala variant in MYH7 has not been previously reported in individuals wit h cardiomyopathy or in large population studies. This variant was predicted to b e pathogenic using a computational tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jo rdan 2011). Although glycine (Gly) at position 56 is fairly well conserved in m ammals and evolutionarily distant species, the mallard duck carries an alanine ( Ala) at this position, raising the possibility that this change may be tolerated . Additional information is needed to fully assess the clinical significance of the Gly56Ala variant.
Invitae RCV001307082 SCV001496475 uncertain significance Hypertrophic cardiomyopathy 2023-10-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 56 of the MYH7 protein (p.Gly56Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy and/or left ventricular noncompaction (PMID: 33500567; Invitae). ClinVar contains an entry for this variant (Variation ID: 179443). 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.

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