ClinVar Miner

Submissions for variant NC_000011.10:g.47335872C>T

gnomAD frequency: 0.00001  dbSNP: rs398123280
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000078450 SCV000110303 uncertain significance not provided 2015-09-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000474107 SCV000546446 pathogenic Hypertrophic cardiomyopathy 2024-11-24 criteria provided, single submitter clinical testing This sequence change falls in intron 26 of the MYBPC3 gene. It does not directly change the encoded amino acid sequence of the MYBPC3 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with hypertrophic cardiomyopathy (PMID: 30297972, 33190526; internal data). ClinVar contains an entry for this variant (Variation ID: 92690). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000618232 SCV000737355 likely pathogenic Cardiovascular phenotype 2025-01-06 criteria provided, single submitter clinical testing The c.2737+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 26 in the MYBPC3 gene. This alteration has been reported in multiple unrelated probands with hypertrophic cardiomyopathy (HCM) (Ho CY et al. Circulation, 2018 Oct;138:1387-1398; O'Hare BJ et al. Circ Genom Precis Med, 2020 Dec;13:e003013; GeneDx pers. comm.; Invitae pers. comm.; Ambry internal data). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Color Diagnostics, LLC DBA Color Health RCV001184227 SCV001350167 likely pathogenic Cardiomyopathy 2023-03-14 criteria provided, single submitter clinical testing This variant causes a G to A nucleotide substitution at the +5 position of intron 26 of the MYBPC3 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 30297972, 32841044, 33190526; communication with external laboratories [ClinVar variation ID: 92690]). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000078450 SCV001713561 likely pathogenic not provided 2019-07-08 criteria provided, single submitter clinical testing PVS1_moderate, PM2, PS4_moderate
All of Us Research Program, National Institutes of Health RCV000474107 SCV004830135 likely pathogenic Hypertrophic cardiomyopathy 2023-06-08 criteria provided, single submitter clinical testing This variant causes a G to A nucleotide substitution at the +5 position of intron 26 of the MYBPC3 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 30297972, 32841044, 33190526; communication with external laboratories [ClinVar variation ID: 92690]). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic.

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.