Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001266136 | SCV001444308 | uncertain significance | Inborn genetic diseases | 2020-01-14 | criteria provided, single submitter | clinical testing | The alteration results in an amino acid change: The c.655G>A (p.V219M) alteration is located in coding exon 1 of the B3GALT6 gene. This alteration results from a G to A substitution at nucleotide position 655, causing the valine (V) at amino acid position 219 to be replaced by a methionine (M). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the B3GALT6 c.655G>A alteration was not observed, with coverage at this position. The altered amino acid is conserved throughout evolution: The V219 amino acid is conserved in available vertebrate species. The alteration is predicted benign by in silico models: The V219M alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001341729 | SCV001535615 | uncertain significance | Ehlers-Danlos syndrome, spondylodysplastic type, 2; Spondyloepimetaphyseal dysplasia with joint laxity | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 219 of the B3GALT6 protein (p.Val219Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of B3GALT6-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 568476). 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 C15"). 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. |