ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2555dup (p.Gly853fs)

dbSNP: rs752104988
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003236394 SCV003934391 pathogenic Cardiomyopathy 2023-05-18 criteria provided, single submitter clinical testing Variant summary: MYBPC3 c.2555dupT (p.Gly853ArgfsX31) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 245894 control chromosomes. To our knowledge, no occurrence of c.2555dupT by itself in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. However, this variant has been reported in combination with c.2557G>T and classified as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017976 SCV004848058 pathogenic Hypertrophic cardiomyopathy 2017-05-12 criteria provided, single submitter clinical testing The p.Gly853fs variant in MYBPC3 has been identified in 1 individual with HCM (Van Driest 2004) and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 853 and leads to a premature termination codon 31 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the MYBPC3 gene is an established disease mechanism in individuals with HCM. In summary, this variant meets criteria to be classified as pathogenic.

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