Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV001333961 | SCV001526680 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 | 2018-12-26 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Invitae | RCV001854940 | SCV002294463 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 | 2022-06-29 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 287 of the POMGNT1 protein (p.Ile287Ser). This variant is present in population databases (rs200863680, gnomAD 0.007%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 26908613). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 254270). 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 not expected to disrupt POMGNT1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Revvity Omics, |
RCV003133196 | SCV003811740 | uncertain significance | not provided | 2019-08-13 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479082 | SCV004222701 | uncertain significance | not specified | 2023-11-15 | criteria provided, single submitter | clinical testing | Variant summary: POMGNT1 c.860T>G (p.Ile287Ser) results in a non-conservative amino acid change in 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 1.2e-05 in 251462 control chromosomes (gnomAD). c.860T>G has been reported in the literature in the compound heterozygous state in trans with a pathogenic variant in two siblings affected with autosomal recessive retinitis pigmentosa, without additional clinical features suggestive of muscular dystrophy, and it segregated with this phenotype in the family (Xu_2016). This report does not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy. At least one publication reports experimental evidence evaluating an impact on protein function (Xu_2016). The most pronounced variant effect results in 10%-<30% of WT enzyme activity. The following publications have been ascertained in the context of this evaluation (PMID: 36819107, 26908613). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV000240954 | SCV000299360 | pathogenic | Retinitis pigmentosa 76 | 2016-09-20 | no assertion criteria provided | literature only |