ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.436G>A (p.Ala146Thr) (rs397517903)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206666 SCV000262069 uncertain significance Charcot-Marie-Tooth disease, type 2 2016-03-05 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 146 of the LMNA protein (p.Ala146Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (rs397517903, ExAC no frequency). This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 24503780) and seen in affected family members. However, this is insufficient evidence to conclude whether this variant segregates with disease or not. ClinVar contains an entry for this variant (Variation ID: 48065). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is absent from population databases, is predicted to be deleterious, and has been reported previously in a patient with dilated cardiomyopathy. However, in the absence of confirmed segregation or functional studies, at this time this change has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000041348 SCV000065041 uncertain significance not specified 2016-01-14 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.