ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1895del (p.Met632fs) (rs397515934)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770344 SCV000901778 pathogenic Cardiomyopathy 2017-02-09 criteria provided, single submitter clinical testing
GeneDx RCV000158356 SCV000208291 pathogenic not provided 2014-07-23 criteria provided, single submitter clinical testing Although the c.1895delT mutation in the MYBPC3 gene has not been reported to our knowledge, this mutation causes a shift in reading frame starting at codon Methionine 632, changing it to an Arginine, and creating a premature stop codon at position 31 of the new reading frame, denoted p.Met632ArgfsX31. This mutation is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift mutations in the MYBPC3 gene have been reported in association with cardiomyopathy. Furthermore, the c.1895delT mutation was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, c.1895delT in the MYBPC3 gene is interpreted as a disease-causing mutation.
Invitae RCV000528888 SCV000623537 pathogenic Hypertrophic cardiomyopathy 2018-06-02 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 19 of the MYBPC3 mRNA (c.1895delT), causing a frameshift at codon 632. This creates a premature translational stop signal (p.Met632Argfs*31) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic. This particular variant has been reported in two individuals affected with hypertrophic cardiomyopathy (PMID: 25611685). ClinVar contains an entry for this variant (Variation ID: 42581). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000528888 SCV000059097 pathogenic Hypertrophic cardiomyopathy 2011-11-08 criteria provided, single submitter clinical testing The Met632fs variant has not been reported in the literature. This variant has b een identified by our laboratory in two probands with HCM and has segregated wit h disease in two affected family members. In addition, this variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 632 and leads to a premature stop codon 31 amino acids downstream. Thi s alteration is then predicted to lead to a truncated or absent protein. Loss of function of the MYBPC3 gene is an established disease mechanism in HCM. Therefo re, the Met632fs variant meets our criteria for pathogenicity (http://pcpgm.part

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