Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000116053 | SCV000149962 | uncertain significance | not provided | 2014-02-26 | 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.3250G>C at the cDNA level, p.Val1084Leu (V1084L) at the protein level, and results in the change of a Valine to a Leucine (GTG>CTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PALLD Val1084Leu was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Valine and Leucine share similar properties, this is considered a conservative amino acid substitution and is unlikely to affect protein integrity. PALLD Val1084Leu occurs at a position that is well conserved across species and is located in the Ig-like C2-type 3 domain (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on 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. |
Invitae | RCV001053240 | SCV001217491 | uncertain significance | Pancreatic adenocarcinoma | 2021-10-20 | criteria provided, single submitter | clinical testing | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). ClinVar contains an entry for this variant (Variation ID: 128109). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. This variant is present in population databases (rs368806050, ExAC 0.001%). This sequence change replaces valine with leucine at codon 597 of the PALLD protein (p.Val597Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. |