Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129631 | SCV000184424 | uncertain significance | Hereditary cancer-predisposing syndrome | 2013-09-27 | criteria provided, single submitter | clinical testing | ​The p.K49R variant (also known as c.146A>G) is located in coding exon 2 of the APC gene. This alteration results from a A to G substitution at nucleotide position 146. The lysine at codon 49 is replaced by arginine, 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. To date, this alteration has been detected with an allele frequency of approximately 0.02% (greater than 6000 alleles tested) in our clinical cohort (includes this individual). Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damging, but tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.I391V remains unclear. |