ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.851T>C (p.Leu284Pro)

dbSNP: rs886043260
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000390988 SCV000339162 uncertain significance not provided 2016-02-18 criteria provided, single submitter clinical testing
Invitae RCV000693559 SCV000821432 pathogenic Charcot-Marie-Tooth disease type 2 2022-08-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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: 285938). This missense change has been observed in individual(s) with autosomal dominant limb-girdle muscular dystrophy and cardiomyopathy (PMID: 22491857). 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 284 of the LMNA protein (p.Leu284Pro).
3billion RCV002250618 SCV002521531 pathogenic Congenital muscular dystrophy due to LMNA mutation 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. Functional studies provide supporting evidence of the variant having a damaging effect on the gene or gene product (PMID: 22491857). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.73; 3Cnet: 0.87). The variant has been previously reported as de novo in a similarly affected individual (PMID: 22491857). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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