Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587903 | SCV000694004 | uncertain significance | not provided | 2016-09-26 | criteria provided, single submitter | clinical testing | Variant summary: The APC c.193C>A (p.Gln65Lys) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121020 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. One clinical lab has classified the variant as a VUS. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |
| Labcorp Genetics |
RCV004567444 | SCV002157452 | uncertain significance | Familial adenomatous polyposis 1 | 2021-10-05 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 217938). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with lysine at codon 65 of the APC protein (p.Gln65Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. |
| Ambry Genetics | RCV002408885 | SCV002722749 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-24 | criteria provided, single submitter | clinical testing | The p.Q65K variant (also known as c.193C>A), located in coding exon 2 of the APC gene, results from a C to A substitution at nucleotide position 193. The glutamine at codon 65 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Mayo Clinic Laboratories, |
RCV000202251 | SCV000256934 | uncertain significance | not specified | no assertion criteria provided | research |