ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1021G>A (p.Gly341Ser)

gnomAD frequency: 0.00003  dbSNP: rs397515881
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035364 SCV000059012 uncertain significance not specified 2020-08-04 criteria provided, single submitter clinical testing The p.Gly341Ser variant in MYBPC3 has been previously reported in 2 individuals with hypertrophic cardiomyopathy (HCM; Alfares 2015 PMID: 25611685, Walsh 2017 PMID: 27532257, LMM data). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 42499) and has been identified in 0.017% (6/35298) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Gly341Ser variant is uncertain. ACMG/AMP Criteria applied: PP3, PS4_Supporting.
GeneDx RCV000766320 SCV000490638 uncertain significance not provided 2023-07-05 criteria provided, single submitter clinical testing Identified in patients with HCM in the published literature (Alfares et al., 2015; Walsh et al., 2017; Thompson et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 25611685, 33782553)
Invitae RCV000703423 SCV000832321 uncertain significance Hypertrophic cardiomyopathy 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 341 of the MYBPC3 protein (p.Gly341Ser). This variant is present in population databases (rs397515881, gnomAD 0.02%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25611685, 27532257, 33782553, 36264615). ClinVar contains an entry for this variant (Variation ID: 42499). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Illumina Laboratory Services, Illumina RCV001106266 SCV001263312 uncertain significance Hypertrophic cardiomyopathy 4 2018-11-29 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001106267 SCV001263313 uncertain significance Left ventricular noncompaction 10 2018-11-29 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color Diagnostics, LLC DBA Color Health RCV001190893 SCV001358528 uncertain significance Cardiomyopathy 2023-04-07 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 341 of the MYBPC3 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least 2 individuals affected with hypertrophic cardiomyopathy (PMID: 25611685, 27532257, 32841044). This variant has been identified in 14/280044 chromosomes 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.
Ambry Genetics RCV003362669 SCV004084128 uncertain significance Cardiovascular phenotype 2023-09-06 criteria provided, single submitter clinical testing The p.G341S variant (also known as c.1021G>A), located in coding exon 12 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 1021. The glycine at codon 341 is replaced by serine, an amino acid with similar properties. This alteration has been reported in hypertrophic cardiomyopathy (HCM) cohorts (Page SP et al. Circ Cardiovasc Genet, 2012 Apr;5:156-66; Alfares AA et al. Genet Med, 2015 Nov;17:880-8; Walsh R et al. Genet Med, 2017 02;19:192-203). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001190893 SCV004239332 uncertain significance Cardiomyopathy 2023-06-01 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.