Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000566225 | SCV000667634 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-21 | criteria provided, single submitter | clinical testing | The p.Q8* pathogenic mutation (also known as c.22C>T), located in coding exon 1 of the APC gene, results from a C to T substitution at nucleotide position 22. This changes the amino acid from a glutamine to a stop codon within coding exon 1. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay; however, this alteration and other loss-of-function alterations that occur at the extreme N-terminus of APC have been observed in numerous individuals who do not have a personal or family history that is consistent with or suggestive of APC associated disease (Ambry internal data). This suggests the use of an alternate translation initiation site which could be imparted by the second, in-frame methionine located at p.M18. Evidence for the use of this methionine or the functional characteristics of an APC protein lacking amino acids 1-17 have not been published. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |