Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001231297 | SCV001403814 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2024-02-02 | criteria provided, single submitter | clinical testing | This sequence change affects codon 171 of the LMNA mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LMNA protein. RNA analysis indicates that this variant induces altered splicing and likely results in the gain of 15 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of autosomal dominant LMNA-related conditions (PMID: 14569138; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 66902). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in the activation of a cryptic splice site in intron 2 (PMID: 14569138). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057412 | SCV000088526 | not provided | not provided | no assertion provided | not provided |