ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.74G>T (p.Arg25Leu) (rs61578124)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236179 SCV000292959 uncertain significance not provided 2019-01-15 criteria provided, single submitter clinical testing The R25L variant of uncertain significance in the LMNA gene has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R25L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species. Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in this residue (R25G, R25C, R25P) and missense variants in nearby residues (S22L, T27I, T27S, R28W, R28Q) have been reported in the Human Gene Mutation Database in association with LMNA-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein.
Invitae RCV001079756 SCV000657821 likely benign Charcot-Marie-Tooth disease, type 2 2019-10-12 criteria provided, single submitter clinical testing
Color RCV001182288 SCV001347688 uncertain significance Cardiomyopathy 2020-01-06 criteria provided, single submitter clinical testing

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