ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.906-7G>T

gnomAD frequency: 0.00036  dbSNP: rs397516079
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035676 SCV000059327 likely benign not specified 2020-08-12 criteria provided, single submitter clinical testing The c.906-7G>T variant in MYBPC3 is classified as likely benign it has been identified in 0.06% (70/122142) of European chromosomes by gnomAD ( Computational splice prediction tools as well as in vitro RNA splicing assays do not predict and impact on splicing (Frisso 2016 PMID: 27834932). ACMG/AMP Criteria applied: BS1, BP4, BP7.
GeneDx RCV000035676 SCV000209459 uncertain significance not specified 2013-11-20 criteria provided, single submitter clinical testing The variant is found in HCM panel(s).
Invitae RCV001083307 SCV000623627 likely benign Hypertrophic cardiomyopathy 2024-01-27 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000625029 SCV000743568 likely benign Hypertrophic cardiomyopathy 4 2016-10-27 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000625029 SCV000744862 benign Hypertrophic cardiomyopathy 4 2017-05-31 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000770373 SCV000901814 likely benign Cardiomyopathy 2021-06-01 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000530779 SCV001148282 likely benign not provided 2020-12-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000770373 SCV001357000 likely benign Cardiomyopathy 2019-11-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000035676 SCV002600394 likely benign not specified 2022-10-10 criteria provided, single submitter clinical testing Variant summary: MYBPC3 c.906-7G>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. In a mini gene assay, the variant was reported to have no impact on splicing (Frisso_2016). The variant allele was found at a frequency of 0.00028 in 230196 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MYBPC3 causing Hypertrophic Cardiomyopathy (0.00028 vs 0.001), allowing no conclusion about variant significance. c.906-7G>T has been reported in the literature in at least one individual affected with Hypertrophic Cardiomyopathy, without strong evidence for causality (Frisso_2016). This report does not provide unequivocal conclusions about association of the variant with Hypertrophic Cardiomyopathy. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Six submitters classified the variant as likely benign/benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences RCV004549436 SCV004766296 likely benign MYBPC3-related disorder 2020-05-05 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center RCV000035676 SCV001922600 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000530779 SCV001954550 likely benign not provided no assertion criteria provided clinical testing

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