Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001854176 | SCV002258264 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-03-08 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects LMNA function (PMID: 20980393). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 66898). This missense change has been observed in individual(s) with autosomal dominant Emery-Dreifuss muscular dystrophy and/or autosomal dominant LMNA-related conditions (PMID: 12649505; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 140 of the LMNA protein (p.Leu140Pro). |
Epithelial Biology; Institute of Medical Biology, |
RCV000057402 | SCV000088515 | not provided | not provided | no assertion provided | not provided |