Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003581576 | SCV004292927 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-01-03 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects LMNA function (PMID: 18031308). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LMNA protein function. ClinVar contains an entry for this variant (Variation ID: 66866). This missense change has been observed in individual(s) with clinical features of LMNA-related conditions (PMID: 18031308). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 591 of the LMNA protein (p.Cys591Phe). |
Epithelial Biology; Institute of Medical Biology, |
RCV000057358 | SCV000088471 | not provided | not provided | no assertion provided | not provided |