ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2332G>A (p.Asp778Asn)

dbSNP: rs730880895
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621047 SCV000736358 uncertain significance Cardiovascular phenotype 2023-09-28 criteria provided, single submitter clinical testing The p.D778N variant (also known as c.2332G>A), located in coding exon 19 of the MYH7 gene, results from a G to A substitution at nucleotide position 2332. The aspartic acid at codon 778 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been observed in individuals with MYH7-related-cardiomyopathy (Lu C et al. J Transl Med, 2018 Aug;16:241). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769460 SCV000900854 likely pathogenic Cardiomyopathy 2015-09-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001172073 SCV001335010 likely pathogenic not provided 2023-08-01 criteria provided, single submitter clinical testing MYH7: PM1, PM2, PM5, PP1:Moderate, PP3
Invitae RCV001850224 SCV002156497 pathogenic Hypertrophic cardiomyopathy 2023-08-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 778 of the MYH7 protein (p.Asp778Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 30165862; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 181369). 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. This variant disrupts the p.Asp778 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12566107, 15358028, 21896538, 22112859; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics Laboratory, Region Ostergotland RCV002251738 SCV002522539 likely pathogenic Hypertrophic cardiomyopathy 1 2020-02-05 criteria provided, single submitter clinical testing PM1, PM2, PM5, PP3

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