Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001177454 | SCV001341678 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces tryptophan with glycine at codon 2101 of the APC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV003769905 | SCV002250962 | uncertain significance | Familial adenomatous polyposis 1 | 2021-04-05 | criteria provided, single submitter | clinical testing | 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 919325). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with glycine at codon 2101 of the APC protein (p.Trp2101Gly). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and glycine. |
Ambry Genetics | RCV001177454 | SCV002657232 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-29 | criteria provided, single submitter | clinical testing | The p.W2101G variant (also known as c.6301T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 6301. The tryptophan at codon 2101 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |