ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.139_140insCG (p.Arg47fs) (rs1555152455)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599468 SCV000709906 pathogenic not provided 2018-02-28 criteria provided, single submitter clinical testing The c.139_140insCG pathogenic variant in the ACVRL1 gene has been identified in six members of a Danish family with HHT, where three members were clinically diagnosed with HHT per Curacao criteria, and three members were diagnosed with HHT as a result of genetic testing (Torring et al., 2014). This variant causes a shift in reading frame starting at codon arginine 47, changing it to a proline, and creating a premature stop codon at position 8 of the new reading frame, denoted p.Arg47ProfsX8. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Several other frameshift variants in the ACVRL1 gene have been reported in the Human Gene Mutation Database in association with HHT (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.139_140insCG variant has not been observed in large population cohorts (Lek et al., 2016).

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