Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035409 | SCV000059057 | likely benign | not specified | 2015-06-12 | criteria provided, single submitter | clinical testing | p.Gly507Arg in exon 17 of MYBPC3: This variant is not expected to have clinical significance because it has been identified in 0.6% (54/9808) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs35736435). |
Gene |
RCV000587761 | SCV000170431 | likely benign | not provided | 2021-03-15 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 23299917, 12974739, 21310275, 15519027, 17560888, 23217326, 22763267, 23233322, 25637381, 22995991, 24055113, 23820649, 26332594, 30188508) |
CSER _CC_NCGL, |
RCV000148661 | SCV000190385 | likely benign | Primary familial hypertrophic cardiomyopathy | 2014-06-01 | criteria provided, single submitter | research | |
Eurofins Ntd Llc |
RCV000035409 | SCV000203047 | benign | not specified | 2014-01-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001081053 | SCV000253164 | benign | Hypertrophic cardiomyopathy | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Soonchunhyang University Bucheon Hospital, |
RCV000490352 | SCV000267407 | uncertain significance | Hypertrophic cardiomyopathy 4 | 2016-03-18 | criteria provided, single submitter | reference population | |
Prevention |
RCV000035409 | SCV000303185 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Ambry Genetics | RCV000242061 | SCV000319842 | likely benign | Cardiovascular phenotype | 2018-06-01 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000035409 | SCV000696314 | likely benign | not specified | 2021-11-22 | criteria provided, single submitter | clinical testing | Variant summary: MYBPC3 c.1519G>A (p.Gly507Arg) results in a non-conservative amino acid change located in the Immunoglobulin subtype 2 domain (IPR003598) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0006 in 249266 control chromosomes, predominantly at a frequency of 0.0054 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 5.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYBPC3 causing Hypertrophic Cardiomyopathy (HCM) phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1519G>A has been reported in the literature in sequencing studies of individuals affected with and/or undergoing multigene panel testing for Hypertrophic Cardiomyopathy (example, Erdmann_2003, Kassem_2013, Lakdawala_2012, Liu_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hypertrophic Cardiomyopathy. At-least two co-occurrences with other pathogenic variant(s) have been observed at our laboratory (HCM-MYBPC3 c.2308G>A, p.Asp770Asn; Transthyretin Amylidosis-TTR c.424G>A, p.Val142Ile), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with a predominant consensus leaning towards benign/likely benign (n=9) (VUS, n=1). Some submitters cite overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as likely benign. |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000035409 | SCV000740369 | likely benign | not specified | 2017-07-12 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000776189 | SCV000911318 | likely benign | Cardiomyopathy | 2018-04-13 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000852652 | SCV000995357 | benign | Familial amyloid neuropathy | 2019-05-20 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000490352 | SCV001138303 | benign | Hypertrophic cardiomyopathy 4 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000776189 | SCV001333616 | benign | Cardiomyopathy | 2018-12-14 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000587761 | SCV004564271 | likely benign | not provided | 2023-03-28 | criteria provided, single submitter | clinical testing |