Submissions for variant NM_000256.3(MYBPC3):c.2414G>A (p.Gly805Asp)

dbSNP: rs730880566

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158156	SCV000208091	pathogenic	not provided	2013-04-05	criteria provided, single submitter	clinical testing	p.Gly805Asp (GGC>GAC): c.2414 G>A in exon 25 of the MYBPC3 gene (NM_000256.3). While the Gly805Asp mutation in the MYBPC3 gene has not been reported to our knowledge, a mutation affecting this same codon, Gly805Ser, has been reported in association with HCM (Kubo et al., 2011). Additionally, mutations in nearby residues (Trp792Arg, Arg810His) have been reported in association with HCM, further supporting the functional importance of this codon and this region of the protein. Gly805Asp results in a non-conservative amino acid substitution of non-polar Glycine residue with a negatively charged Aspartic acid residue at a position that is conserved across species. In silico analysis predicts Gly805Asp is probably damaging to the protein structure/function. Furthermore, Gly805Asp was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, Gly805Asp in the MYBPC3 gene is interpreted as a likely disease-causing mutation. Mutations in the MYBPC3 gene have been reported in 20%-30% of patients with autosomal dominant familial hypertrophic cardiomyopathy, and have been reported less frequently in patients with autosomal dominant familial dilated cardiomyopathy (Cirino A et al., 2011; Hershberger R et al., 2009). The variant is found in HCM panel(s).
Ambry Genetics	RCV002453534	SCV002735978	uncertain significance	Cardiovascular phenotype	2020-10-02	criteria provided, single submitter	clinical testing	The p.G805D variant (also known as c.2414G>A), located in coding exon 25 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 2414. This variant impacts the first base pair of coding exon 25. The glycine at codon 805 is replaced by aspartic acid, an amino acid with similar properties. 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.