ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1280G>A (p.Arg427His) (rs747139279)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000235626 SCV000614025 uncertain significance not specified 2016-11-25 criteria provided, single submitter clinical testing
GeneDx RCV000767210 SCV000292898 uncertain significance not provided 2015-05-21 criteria provided, single submitter clinical testing The R427H variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. The R427H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Missense mutations in nearby residues (R419C, L421P, R435C) and in the same residue (R427G) 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. However, the R427H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved only in mammals. Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.

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