ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.658C>T (p.Arg220Cys) (rs370134870)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000247356 SCV000320673 uncertain significance Cardiovascular phenotype 2015-12-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000594818 SCV000704256 uncertain significance not provided 2016-12-28 criteria provided, single submitter clinical testing
Invitae RCV000800454 SCV000940169 uncertain significance Charcot-Marie-Tooth disease, type 2 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 220 of the LMNA protein (p.Arg220Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs370134870, ExAC 0.009%). This variant has been observed in an individual affected with Emery-Dreifuss muscular dystrophy (PMID: 26573435). ClinVar contains an entry for this variant (Variation ID: 264626). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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