Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute for Genomic Medicine, |
RCV000779598 | SCV000914236 | uncertain significance | Lethal skeletal dysplasia | 2019-05-23 | criteria provided, single submitter | research | This variant has been observed in 1 out of 120,473 gnomAD individuals (1 heterozygote, MAF=0.00000415), making it extremely rare. It is predicted to cause a missense change in the glycosyltransferase domain, and classified as damaging by a majority of in silico tools. In vitro enzyme assays confirmed a total lack of enzyme activity for this variant. |
| Invitae | RCV001856177 | SCV002168511 | uncertain significance | Ehlers-Danlos syndrome progeroid type | 2021-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with arginine at codon 133 of the B4GALT7 protein (p.Gln133Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with B4GALT7-related conditions (PMID: 31278392). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 632558). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects B4GALT7 function (PMID: 31278392). 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. |
| Gene |
RCV002462129 | SCV002757014 | pathogenic | not provided | 2022-11-16 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a impaired protein localization and activity (Mihalic Mosher et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31278392, 34193099) |
| OMIM | RCV003446432 | SCV004171731 | pathogenic | Ehlers-Danlos syndrome, spondylodysplastic type, 1 | 2023-11-30 | no assertion criteria provided | literature only |