Submissions for variant NM_000256.3(MYBPC3):c.2800C>T (p.Leu934=)

gnomAD frequency: 0.00001  dbSNP: rs367980215

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035527	SCV000059177	likely benign	not specified	2012-07-24	criteria provided, single submitter	clinical testing	Leu934Leu in exon 27 of MYBPC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 1/8304 European Am erican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). Leu934Leu in exon 27 of MYBPC3 (allele fre quency = 1/8304) **
Labcorp Genetics (formerly Invitae), Labcorp	RCV000527686	SCV000623575	likely benign	Hypertrophic cardiomyopathy	2024-11-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621573	SCV000740017	likely benign	Cardiovascular phenotype	2017-01-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769313	SCV000900691	likely benign	Cardiomyopathy	2023-04-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769313	SCV000913825	benign	Cardiomyopathy	2018-10-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001103021	SCV001259731	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001104919	SCV001261825	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.
Phosphorus, Inc.	RCV000035527	SCV002073396	likely benign	not specified	2022-01-17	criteria provided, single submitter	clinical testing	This synonymous variant has occurred in GnomAD with a total MAF of 0.0086% and with the highest MAF of 0.1935% in the Ashkenazi Jewish population. This position is not conserved. In silico splicing algorithm predicted no impact on splicing, but no functional studies were performed to confirm this prediction. This variant NM_000256.3(MYBPC3):c.2800C>T (p.Leu934=) is present in the ClinVar database (ID: 42658). The variant has not occurred in the literature in association with the disease. Considering that the variant has a relatively high frequency in a subpopulation, it has been classified as Likely Benign.
All of Us Research Program, National Institutes of Health	RCV000527686	SCV004836712	benign	Hypertrophic cardiomyopathy	2024-01-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV004808561	SCV005435174	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	MYBPC3: BP4, BS1