ClinVar Miner

Submissions for variant NM_000252.3(MTM1):c.1132G>A (p.Gly378Arg)

dbSNP: rs587783755
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146376 SCV000193660 pathogenic Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000146376 SCV001404208 pathogenic Severe X-linked myotubular myopathy 2019-10-25 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with myotubular myopathy (PMID: 8640223, 12031625, 10714588, 28685322). In at least one individual the variant was observed to be de novo. This variant is also known as G1186A, G396R in the literature. ClinVar contains an entry for this variant (Variation ID: 158897). This variant has been reported to affect MTM1 protein function (PMID: 10900271, 12118066). For these reasons, this variant has been classified as Pathogenic. This sequence change replaces glycine with arginine at codon 378 of the MTM1 protein (p.Gly378Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine.
Ambry Genetics RCV001266066 SCV001444238 likely pathogenic Inborn genetic diseases 2018-04-10 criteria provided, single submitter clinical testing
3billion RCV000146376 SCV005903848 pathogenic Severe X-linked myotubular myopathy 2023-12-08 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.94 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.97 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000158897 /PMID: 8640223). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 10714588, 12031625, 28685322, 8640223). Different missense changes at the same codon (p.Gly378Glu, p.Gly378Val) have been reported to be associated with MTM1 related disorder (ClinVar ID: VCV001028156 /PMID: 10063835). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

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.