Submissions for variant NM_000256.3(MYBPC3):c.1008C>T (p.Ile336=)

dbSNP: rs397515880

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035363	SCV000059011	likely benign	not specified	2012-11-15	criteria provided, single submitter	clinical testing	Ile336Ile in exon 12 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. Ile336Ile in exon 12 of MYBPC3 (allele fre quency = n/a)
Ambry Genetics	RCV000241564	SCV000317964	likely benign	Cardiovascular phenotype	2021-09-02	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.
GeneDx	RCV001711147	SCV000513752	likely benign	not provided	2018-07-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28679633)
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000607104	SCV000744856	likely benign	Hypertrophic cardiomyopathy 4	2015-09-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000629171	SCV000750087	likely benign	Hypertrophic cardiomyopathy	2023-01-25	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769353	SCV000900741	likely benign	Cardiomyopathy	2016-03-15	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769353	SCV004358753	uncertain significance	Cardiomyopathy	2023-07-27	criteria provided, single submitter	clinical testing	This synonymous variant causes a nucleotide substitution but does not change the encoded amino acid at codon 336 of the MYBPC3 protein. Splice prediction tools are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in homozygous state in an individual affected with hypertrophic cardiomyopathy, cryptorchidism, and hypotonia (doi:10.34087/cbusbed.1052808). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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.
All of Us Research Program, National Institutes of Health	RCV000629171	SCV004834690	uncertain significance	Hypertrophic cardiomyopathy	2023-08-15	criteria provided, single submitter	clinical testing	This synonymous variant causes a nucleotide substitution but does not change the encoded amino acid at codon 336 of the MYBPC3 protein. Splice prediction tools are inconclusive regarding the impact of this variant on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in homozygous state in an individual affected with hypertrophic cardiomyopathy, cryptorchidism, and hypotonia (doi:10.34087/cbusbed.1052808). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000607104	SCV000733055	likely benign	Hypertrophic cardiomyopathy 4		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001711147	SCV001957742	likely benign	not provided		no assertion criteria provided	clinical testing