ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.419T>C (p.Leu140Pro)

dbSNP: rs60652225
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001854176 SCV002258264 pathogenic Charcot-Marie-Tooth disease type 2 2024-09-06 criteria provided, single submitter clinical testing 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). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant Emery-Dreifuss muscular dystrophy and/or clinical features of autosomal dominant arrhythmogenic cardiomyopathy (PMID: 12649505; internal data). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 66898). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt LMNA protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects LMNA function (PMID: 20980393). For these reasons, this variant has been classified as Pathogenic.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057402 SCV000088515 not provided not provided no assertion provided not provided

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