Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000116038 | SCV000149947 | uncertain significance | not provided | 2014-02-10 | criteria provided, single submitter | clinical testing | PALLD has been only recently described in association with cancer predisposition and the risks are not well understood. This variant is denoted PALLD c.1040C>T at the cDNA level, p.Thr347Met (T347M) at the protein level, and results in the change of a Threonine to a Methionine (ACG>ATG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PALLD Thr347Met was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a non-conservative substitution in which a neutral polar amino acid is replaced with a neutral non-polar one, altering a position that is highly variable throughout evolution and is located in within the Ig-like C2-type 1 domain (Uniprot). Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the PALLD gene, remain unclear. |
Illumina Laboratory Services, |
RCV000330846 | SCV000448471 | benign | Pancreatic cancer, susceptibility to, 1 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |