Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002014042 | SCV002298549 | uncertain significance | Pancreatic adenocarcinoma | 2021-05-19 | 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C65". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PALLD-related conditions. This variant is present in population databases (rs771536528, ExAC 0.003%). This sequence change replaces asparagine with histidine at codon 576 of the PALLD protein (p.Asn576His). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and histidine. |
Ambry Genetics | RCV004046678 | SCV002609239 | uncertain significance | not specified | 2022-10-24 | criteria provided, single submitter | clinical testing | The p.N1063H variant (also known as c.3187A>C), located in coding exon 18 of the PALLD gene, results from an A to C substitution at nucleotide position 3187. The asparagine at codon 1063 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |