Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213566 | SCV000276884 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-06-26 | criteria provided, single submitter | clinical testing | The p.N2604K variant (also known as c.7812C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 7812. The asparagine at codon 2604 is replaced by lysine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 32000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. 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 p.N2604K remains unclear. |
| Invitae | RCV003650499 | SCV001393462 | uncertain significance | Familial adenomatous polyposis 1 | 2019-07-24 | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 232691). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with lysine at codon 2604 of the APC protein (p.Asn2604Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. |