Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003765284 | SCV000254041 | uncertain significance | Familial adenomatous polyposis 1 | 2019-06-07 | criteria provided, single submitter | clinical testing | In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant has not been published in the literature and is not present in population databases. This sequence change replaces asparagine with aspartic acid at codon 2618 of the APC protein (p.Asn2618Asp). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and aspartic acid. |
Color Diagnostics, |
RCV000775352 | SCV000909635 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-21 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 2618 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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. |