Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216246 | SCV000276899 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-03 | criteria provided, single submitter | clinical testing | The p.T18P variant (also known as c.52A>C), located in coding exon 1 of the CDKN2A gene, results from an A to C substitution at nucleotide position 52. The threonine at codon 18 is replaced by proline, an amino acid with highly similar properties. This alteration has been reported in at least one individual with suspected familial pancreatic cancer and was classified as a variant of unknown significance by authors (Zhen DB et al, Genet. Med. 2015 Jul; 17(7):569-77; Chaffee KG. et al, Genet Med. 2018 01;20(1):119-127). One functional study reported this variant as deleterious based on in vitro assessment of impact on proliferation in human pancreatic cancer cell lines. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by BayesDel in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |