Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000599487 | SCV000710281 | pathogenic | not provided | 2018-01-02 | criteria provided, single submitter | clinical testing | Although the c.978dupA pathogenic variant in the LMNA gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon leucine 327, changing it to a threonine, and creating a premature stop codon at position 4 of the new reading frame, denoted p.Leu327ThrfsX4. 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. Many other frameshift variants in the LMNA gene have been reported in Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), and loss-of-function is a known mechanism of disease for this gene. Furthermore, the c.978dupA variant has not been observed in large population cohorts (Lek et al., 2016). |