Submissions for variant NM_000256.3(MYBPC3):c.3315C>A (p.Ala1105=)

gnomAD frequency: 0.00003  dbSNP: rs200372325

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035577	SCV000059227	likely benign	not specified	2010-11-30	criteria provided, single submitter	clinical testing	This variant is not expected to have clinical significance because it does not a lter an amino acid residue and is not located near a splice junction. Therefore, it is unlikely that this variant is disease-causing.
Invitae	RCV000629112	SCV000750026	benign	Hypertrophic cardiomyopathy	2023-12-13	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771378	SCV000903680	benign	Cardiomyopathy	2018-07-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001105979	SCV001263003	benign	Left ventricular noncompaction 10	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001105980	SCV001263004	uncertain significance	Hypertrophic cardiomyopathy 4	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV001311761	SCV001502060	likely benign	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002321502	SCV002605789	likely benign	Cardiovascular phenotype	2020-11-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003964842	SCV004786083	likely benign	MYBPC3-related condition	2020-08-17	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).