ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.127G>A (p.Ala43Thr) (rs60446065)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000057262 SCV000293392 likely pathogenic not provided 2017-01-10 criteria provided, single submitter clinical testing The A43T variant has been reported previously in an individual with Emery-Dreifuss muscular dystrophy (EDMD) type 2 who was heterozygous for this change and did not have another identifiable LMNA variant; however, information about parental testing was not provided and functional characterization of the variant was not performed (Brown et al., 2001). It 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 A43T 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, multiple missense variants in nearby residues 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 likely pathogenic; however, the possibility that it is benign cannot be excluded.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000057262 SCV000339872 uncertain significance not provided 2018-04-03 criteria provided, single submitter clinical testing
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057262 SCV000088375 not provided not provided no assertion provided not provided

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