Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000457713 | SCV000548863 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-03-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 41 of the LMNA protein (p.Arg41His). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg41 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been observed in individuals with LMNA-related conditions (PMID: 20980393, 29250285), which suggests that this may be a clinically significant amino acid residue. 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: 408994). This missense change has been observed in individual(s) with myopathy (Invitae). In at least one individual the variant was observed to be de novo. |
Ce |
RCV000994129 | SCV001147454 | pathogenic | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing |