Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000081574 | SCV000113505 | uncertain significance | not provided | 2013-11-06 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000550659 | SCV000649942 | likely pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2; Autosomal recessive limb-girdle muscular dystrophy type 2N | 2024-05-07 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 107 of the POMT2 protein (p.Pro107Leu). This variant is present in population databases (rs398124264, gnomAD 0.004%). This missense change has been observed in individuals with clinical features of POMT2-related conditions (PMID: 28973083; Invitae). ClinVar contains an entry for this variant (Variation ID: 95543). 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 POMT2 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Mendelics | RCV000989247 | SCV001139490 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000081574 | SCV001988140 | uncertain significance | not provided | 2018-12-03 | criteria provided, single submitter | clinical testing | Previously identified in a patient who harbored a second POMT2 variant through exome sequencing, however, detailed clinical information about the patient was not provided (Meng et al., 2017); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28973083) |
3billion, |
RCV000989247 | SCV002521801 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.93; 3Cnet: 0.92). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with POMT2 related disorder (PMID: 28973083). However, the evidence of pathogenicity is insufficient at this time and it is classified as auncertain significancein ClinVar (ClinVar ID: VCV000095543) Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. |
Revvity Omics, |
RCV000081574 | SCV003809740 | uncertain significance | not provided | 2023-02-22 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000081574 | SCV004229903 | uncertain significance | not provided | 2023-08-25 | criteria provided, single submitter | clinical testing | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. The variant is located in a region that is considered important for protein function and/or structure. |
Centre de Biologie Pathologie Génétique, |
RCV001252356 | SCV001428108 | uncertain significance | Intellectual disability | 2019-01-01 | no assertion criteria provided | clinical testing |