Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000175324 | SCV000226795 | pathogenic | not provided | 2013-10-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323349 | SCV004029041 | uncertain significance | not specified | 2023-07-26 | criteria provided, single submitter | clinical testing | Variant summary: POMT1 c.1770G>C (p.Gln590His) results in a non-conservative amino acid change located in the Protein O-mannosyl-transferase, C-terminal four TM domain (IPR032421) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251458 control chromosomes. c.1770G>C has been reported in the literature in compound heterozygous individuals affected with congenital muscular dystrophy with intellectual disability (e.g. vanReeuwijk_2006, Messina_2008). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 18513969, 16575835). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Labcorp Genetics |
RCV003764522 | SCV004569711 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy | 2023-01-22 | criteria provided, single submitter | clinical testing | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on POMT1 protein function. ClinVar contains an entry for this variant (Variation ID: 3246). This missense change has been observed in individual(s) with clinical features of muscular dystrophy-dystroglycanopathy (PMID: 16575835, 16717220, 18513969). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs119462986, gnomAD 0.0009%). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 590 of the POMT1 protein (p.Gln590His). |
| OMIM | RCV002286391 | SCV000023560 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 | 2006-05-01 | no assertion criteria provided | literature only |