Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003653385 | SCV000954970 | uncertain significance | Familial adenomatous polyposis 1 | 2022-08-02 | 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: 657857). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs754122018, gnomAD 0.003%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1680 of the APC protein (p.Gln1680Glu). |
| Mendelics | RCV000814557 | SCV001136920 | uncertain significance | Familial adenomatous polyposis 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002345861 | SCV002646323 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-29 | criteria provided, single submitter | clinical testing | The p.Q1680E variant (also known as c.5038C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 5038. The glutamine at codon 1680 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Department of Pathology and Laboratory Medicine, |
RCV000814557 | SCV001552897 | uncertain significance | Familial adenomatous polyposis 1 | no assertion criteria provided | clinical testing | The APC p.Gln1680Glu variant was not identified in the literature nor was it identified in the ClinVar, LOVD 3.0, or UMD-LSDB databases. The variant was identified in dbSNP (ID: rs754122018) as "With Pathogenic allele" however this entry also refers to the T allele at this loci which creates a termination codon. The variant was identified in control databases in 1 of 244862 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the Latino population in 1 of 33510 chromosomes (freq: 0.00003), but not in the African, Other, European, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Gln1680 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |