Submissions for variant NM_000256.3(MYBPC3):c.2965G>A (p.Glu989Lys)

dbSNP: rs727503178

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001187225	SCV001353958	uncertain significance	Cardiomyopathy	2023-12-05	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with lysine at codon 989 of the MYBPC3 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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.
Invitae	RCV001248233	SCV001421703	uncertain significance	Hypertrophic cardiomyopathy	2022-03-09	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 925347). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 989 of the MYBPC3 protein (p.Glu989Lys).
Centogene AG - the Rare Disease Company	RCV001809990	SCV002059649	uncertain significance	Hypertrophic cardiomyopathy 4	2021-05-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002436756	SCV002750103	uncertain significance	Cardiovascular phenotype	2021-09-07	criteria provided, single submitter	clinical testing	The p.E989K variant (also known as c.2965G>A), located in coding exon 28 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 2965. The glutamic acid at codon 989 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.