ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.992G>C (p.Arg331Pro)

dbSNP: rs59301204
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003581578 SCV004292915 likely pathogenic Charcot-Marie-Tooth disease type 2 2023-07-14 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. This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 331 of the LMNA protein (p.Arg331Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant limb-girdle muscular dystrophy (PMID: 17377071). ClinVar contains an entry for this variant (Variation ID: 66963). 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. Experimental studies have shown that this missense change affects LMNA function (PMID: 34862408). This variant disrupts the p.Arg331 amino acid residue in LMNA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19875404, 23349452, 27532257, 28790152, 29382405). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.
CeGaT Center for Human Genetics Tuebingen RCV000057496 SCV004702259 likely pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing LMNA: PM1, PM2, PM5, PS3:Supporting, PS4:Supporting
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057496 SCV000088610 not provided not provided no assertion provided not provided

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