Submissions for variant NM_000256.3(MYBPC3):c.2470G>A (p.Asp824Asn)

dbSNP: rs774442478

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001188245	SCV001355266	uncertain significance	Cardiomyopathy	2025-03-03	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with asparagine at codon 824 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy, who also carried a frameshift variant in the MYH7 gene (DOI: 10.1016/j.ejmhg.2017.05.002). This variant has been identified in 3/249208 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001876205	SCV002176965	uncertain significance	Hypertrophic cardiomyopathy	2023-12-22	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 824 of the MYBPC3 protein (p.Asp824Asn). This variant is present in population databases (rs774442478, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 925971). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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	RCV002451394	SCV002737454	uncertain significance	Cardiovascular phenotype	2021-09-14	criteria provided, single submitter	clinical testing	The p.D824N variant (also known as c.2470G>A), located in coding exon 25 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 2470. The aspartic acid at codon 824 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003989644	SCV004808217	uncertain significance	Hypertrophic cardiomyopathy 4	2024-03-29	criteria provided, single submitter	clinical testing