ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.917T>C (p.Leu306Pro) (rs730882262)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235583 SCV000293170 likely pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing Although the L306P variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge, a variant in the same residue (L306R) has been reported previously in association with an LMNA-related disorder (Alastalo et al., 2015). The L603P 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 L306P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some 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 pathogenic variants in nearby residues (L302P, S303P, K311R, Q312H) 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.Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded
Genetic Services Laboratory,University of Chicago RCV000500335 SCV000595622 likely pathogenic Dilated cardiomyopathy 1A 2013-02-08 criteria provided, single submitter clinical testing

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