ClinVar Miner

Submissions for variant NM_003289.4(TPM2):c.121G>A (p.Glu41Lys)

dbSNP: rs137853306
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001206319 SCV001377621 pathogenic Arthrogryposis, distal, type 1A 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 41 of the TPM2 protein (p.Glu41Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant TPM2-related conditions (PMID: 17846275, 24692096). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12464). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TPM2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects TPM2 function (PMID: 18420702, 22084935, 24039757, 25978979). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000013280 SCV000033527 pathogenic Congenital myopathy 23 2007-09-01 no assertion criteria provided literature only
TPM2 homepage - Leiden Muscular Dystrophy pages RCV000128672 SCV000172312 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.