Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486027 | SCV000573080 | likely pathogenic | not provided | 2019-10-11 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 58 amino acids are lost and replaced with 90 incorrect amino acids |
Invitae | RCV001851252 | SCV002225692 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-11-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with LMNA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the LMNA gene (p.Val607Trpfs*91). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 58 amino acid(s) of the LMNA protein and extend the protein by 32 additional amino acid residues. ClinVar contains an entry for this variant (Variation ID: 423384). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the C-terminus of the LMNA protein. Other variant(s) that disrupt this region (p.Arg654*) have been observed in individuals with LMNA-related conditions (PMID: 30012837). This suggests that this may be a clinically significant region of the protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. |