ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1734del (p.Lys579fs)

dbSNP: rs730880646
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158351 SCV000208286 pathogenic not provided 2014-09-02 criteria provided, single submitter clinical testing Although the c.1734delG mutation in the MYBPC3 gene has not been reported to our knowledge, this mutation causes a shift in reading frame starting at codon Lysine 579, changing it to an Arginine, and creating a premature stop codon at position 12 of the new reading frame, denoted p.K579RfsX12. 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 HCM. Furthermore, the c.1734delG mutation was not observed in approximately 6,300 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.1734delG in the MYBPC3 gene is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000628972 SCV000749882 pathogenic Hypertrophic cardiomyopathy 2023-06-19 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 181073). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with hypertrophic cardiomyopathy (Invitae). This sequence change creates a premature translational stop signal (p.Lys579Argfs*12) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is not present in population databases (gnomAD no frequency).

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