Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002440170 | SCV002752462 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | The p.I981V variant (also known as c.2941A>G), located in coding exon 16 of the PALLD gene, results from an A to G substitution at nucleotide position 2941. The isoleucine at codon 981 is replaced by valine, an amino acid with highly 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. |
| Ambry Genetics | RCV003289511 | SCV003979602 | uncertain significance | Inborn genetic diseases | 2023-05-23 | criteria provided, single submitter | clinical testing | The c.1480A>G (p.I494V) alteration is located in exon 9 (coding exon 8) of the PALLD gene. This alteration results from a A to G substitution at nucleotide position 1480, causing the isoleucine (I) at amino acid position 494 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005098353 | SCV005825888 | uncertain significance | Pancreatic adenocarcinoma | 2024-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 494 of the PALLD protein (p.Ile494Val). This variant is present in population databases (rs746066225, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PALLD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1797920). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |