ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.224C>T (p.Ser75Phe)

dbSNP: rs879253975
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236603 SCV000293014 likely pathogenic not provided 2019-12-16 criteria provided, single submitter clinical testing Not observed [at a significant frequency] in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25163546)
Labcorp Genetics (formerly Invitae), Labcorp RCV002518434 SCV003523249 uncertain significance Charcot-Marie-Tooth disease type 2 2024-08-31 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 75 of the LMNA protein (p.Ser75Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 25163546). ClinVar contains an entry for this variant (Variation ID: 245850). 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%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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