ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.274C>T (p.Leu92Phe)

gnomAD frequency: 0.00001  dbSNP: rs267607560
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000627124 SCV000747927 likely pathogenic Primary familial dilated cardiomyopathy 2017-06-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV002433553 SCV002749331 likely pathogenic Cardiovascular phenotype 2022-04-14 criteria provided, single submitter clinical testing The p.L92F variant (also known as c.274C>T), located in coding exon 1 of the LMNA gene, results from a C to T substitution at nucleotide position 274. The leucine at codon 92 is replaced by phenylalanine, an amino acid with highly similar properties. This variant has been detected in individuals with dilated cardiomyopathy, cardiac arrhythmia, and cardiac conduction system disease (Marschall C et al. Cardiovasc Diagn Ther, 2019 Oct;9:S292-S298; Chami N et al. Can J Cardiol, 2014 Dec;30:1655-61; Millat G et al. Eur J Med Genet Aug;54:e570-5). In addition, this variant has also been detected in an individual with lipodystrophy and cardiac dysrhythmia. Studies of cultured fibroblasts from this individual demonstrated altered nuclei and reduced proliferative activity (Caron M et al. Cell Death Differ, 2007 Oct;14:1759-67; Decaudain A et al. J Clin Endocrinol Metab, 2007 Dec;92:4835-44; Vouillarmet J et al. Can J Diabetes, 2016 Oct;40:376-378l). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057384 SCV000088497 not provided not provided no assertion provided not provided

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