ClinVar Miner

Submissions for variant NM_000252.3(MTM1):c.1244G>A (p.Gly415Glu)

dbSNP: rs587783766
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
Genetic Services Laboratory, University of Chicago RCV000146387 SCV000193671 pathogenic Severe X-linked myotubular myopathy 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV001582610 SCV001813737 likely pathogenic not provided 2021-08-24 criteria provided, single submitter clinical testing Has been reported previously as pathogenic/likely pathogenic variant in association with myotubular myopathy, however, additional information was not provided (Penon et al., 2018); Different missense variant at the same residue, G415V, was identified in a patient with a severe MTM1-related disorder, however, specific clinical and family segregation information was not included (Tsai et al., 2005); This variant is associated with the following publications: (PMID: 30047259)
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000146387 SCV002767077 likely pathogenic Severe X-linked myotubular myopathy 2023-07-17 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with X-linked centronuclear myopathy (MIM#310400). (I) 0109 - This gene is associated with X-linked recessive disease; however, manifesting female carriers of pathogenic variants who present with a range of clinical severity and skewed X-inactivation are increasingly being reported (GeneReviews, PMID: 28685322). (I) 0115 - Variants in this gene are known to have variable expressivity. Female carriers of pathogenic variants have been reported with a range of clinical severity, ranging from severe neonatal and generalized weakness, to milder adult forms (PMID: 28685322). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to glutamic acid. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools and highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated myotubularin-like phosphatase domain (DECIPHER). (I) 0704 – Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. The p.(Gly415Val) variant has been identified in one individual with severe myotubular myopathy (PMID: 15725586). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been classified once as likely pathogenic and once as pathogenic by clinical diagnostic laboratories (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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.