ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.132A>C (p.Glu44Asp)

gnomAD frequency: 0.00002  dbSNP: rs398124244
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000177268 SCV000229112 likely pathogenic not provided 2013-11-27 criteria provided, single submitter clinical testing
Invitae RCV001376971 SCV001574181 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 44 of the POMT1 protein (p.Glu44Asp). This variant is present in population databases (rs398124244, gnomAD 0.004%). This missense change has been observed in individual(s) with congenital muscular dystrophy (PMID: 27159402). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 95456). 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 expected to disrupt POMT1 protein function with a positive predictive value of 95%. This variant disrupts the p.Glu44 amino acid residue in POMT1. Other variant(s) that disrupt this residue have been observed in individuals with POMT1-related conditions (PMID: 27193224), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000177268 SCV002526472 likely pathogenic not provided 2022-04-12 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27159402, 30564623)
Fulgent Genetics, Fulgent Genetics RCV002477237 SCV002782030 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 2022-05-03 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000177268 SCV003813304 likely pathogenic not provided 2022-11-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003155069 SCV003844711 uncertain significance not specified 2023-02-14 criteria provided, single submitter clinical testing Variant summary: POMT1 c.132A>C (p.Glu44Asp) results in a conservative amino acid change located in the glycosyl transferase family 39/83 domain (IPR003342) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251416 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.132A>C has been reported in the literature in the compound heterozygous state in two individuals affected with Dystrophinopathy (O'Grady_2016, Carlson_2017). These data do not allow any strong conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. All laboratories classified the variant as pathogenic (n=1)/likely pathogenic (n=2). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic until additional clinical and/or functional evidence is available.
PreventionGenetics, part of Exact Sciences RCV004529856 SCV004113553 likely pathogenic POMT1-related disorder 2023-04-17 criteria provided, single submitter clinical testing The POMT1 c.132A>C variant is predicted to result in the amino acid substitution p.Glu44Asp. This variant was reported in the compound heterozygous state in an individual with congenital muscular dystrophy (Table e-1 and e-3, Patient ID 102, O'Grady et al. 2016. PubMed ID: 27159402). Of note, another variant impacting the same amino acid was also reported in the compound heterozygous state in an individual with mild congenital muscular dystrophy [c.130G>A (pl.Glu44Lys), Case 3, Yang et al. 2016. PubMed ID: 27193224). This variant is reported in 0.0039% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-134381510-A-C). This variant is interpreted as likely pathogenic.
Baylor Genetics RCV003474682 SCV004204076 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 2022-06-23 criteria provided, single submitter clinical testing

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.