Submissions for variant NM_000256.3(MYBPC3):c.1076AGA[2] (p.Lys361del)

dbSNP: rs775069579

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001180847	SCV001345881	uncertain significance	Cardiomyopathy	2019-04-28	criteria provided, single submitter	clinical testing	This variant causes a deletion of single amino acid at codon 361 of the MYBPC3 protein. Functional assays have not been performed for this variant. Computational splicing tools suggest that this variant may not impact RNA splicing. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/248872 chromosomes 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	RCV001349982	SCV001544352	uncertain significance	Hypertrophic cardiomyopathy	2023-09-25	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 921429). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. This variant is present in population databases (rs775069579, gnomAD 0.004%). This variant, c.1082_1084del, results in the deletion of 1 amino acid(s) of the MYBPC3 protein (p.Lys361del), but otherwise preserves the integrity of the reading frame.
GeneDx	RCV001751320	SCV001987438	uncertain significance	not provided	2019-04-25	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In-frame deletion of one amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003293934	SCV004001273	uncertain significance	Cardiovascular phenotype	2023-06-09	criteria provided, single submitter	clinical testing	The c.1082_1084delAGA variant (also known as p.K361del) is located in coding exon 12 of the MYBPC3 gene. This variant results from an in-frame AGA deletion at nucleotide positions 1082 to 1084. This results in the in-frame deletion of a lysine at codon 361. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.