Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569844 | SCV000667655 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-10-04 | criteria provided, single submitter | clinical testing | The p.P1848T variant (also known as c.5542C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 5542. The proline at codon 1848 is replaced by threonine, an amino acid with highly 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 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 90000 alleles tested) in our clinical cohort. 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. |
| Invitae | RCV003767151 | SCV002126715 | uncertain significance | Familial adenomatous polyposis 1 | 2020-12-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 482413). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 1848 of the APC protein (p.Pro1848Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. |