ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1698+13C>A (rs80338938)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705473 SCV000834472 pathogenic Charcot-Marie-Tooth disease, type 2 2019-07-17 criteria provided, single submitter clinical testing This sequence change falls in intron 10 of the LMNA gene. It does not directly change the encoded amino acid sequence of the LMNA protein. This variant is present in population databases (rs80338938, ExAC 0.2%). This variant has been reported to segregate with dilated cardiomyopathy and conduction defects in a large multigenerational family (PMID: 10580070). This variant is known in the literature as c.1711C>A (p.Arg571Ser) using the alternate transcript NM_005572.3. ClinVar contains an entry for this variant (Variation ID: 14485). A different variant (c.1711_1712delinsTC) giving rise to the same protein effect observed here (Alternate transcript NM_005572.3:p.Arg571Ser) has been reported in an individual affected with lipodystrophy (PMID: 28686329), indicating that this residue may be critical for protein function. A different missense substitution at this codon (Alternate transcript NM_005572.3:p.Arg571Cys) has been reported in an individual affected with muscular dystrophy and peripheral neuropathy (PMID: 15965218). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Color RCV001189216 SCV001356461 uncertain significance Cardiomyopathy 2018-11-15 criteria provided, single submitter clinical testing
OMIM RCV000015574 SCV000035839 pathogenic Dilated cardiomyopathy 1A 1999-12-02 no assertion criteria provided literature only
GeneReviews RCV000015574 SCV000041153 pathologic Dilated cardiomyopathy 1A 2011-04-05 no assertion criteria provided curation Converted during submission to Pathogenic.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057044 SCV000088157 not provided not provided no assertion provided not provided

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.