ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1004_1005inv (p.Arg335Pro) (rs1553265669)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523321 SCV000620446 likely pathogenic not provided 2018-03-30 criteria provided, single submitter clinical testing The c.1004_1005delGGinsCC variant in the LMNA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1004_1005delGGinsCC variant causes an in-frame substitution of Arginine 335 for a Proline, denoted p.Arg335Pro. The c.1004_1005delGGinsCC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This 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. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in the same and nearby residues (R331P, R331Q, S334N, R335W, R335Q, R336Q) 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. We interpret c.1004_1005delGGinsCC as a likely pathogenic variant.

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