ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.130G>A (p.Glu44Lys)

gnomAD frequency: 0.00001  dbSNP: rs1397478363
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001949458 SCV002245603 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy 2023-10-22 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 44 of the POMT1 protein (p.Glu44Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with muscular dystrophy-dystroglycanopathy (PMID: 24491487, 27193224). 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: 1458255). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Glu44 amino acid residue in POMT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27159402). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003475244 SCV004204051 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 2023-11-28 criteria provided, single submitter clinical testing

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