Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001994298 | SCV002274380 | uncertain significance | Familial cancer of breast | 2020-11-05 | 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine 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 been observed in individual(s) with breast cancer (PMID: 28779002). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 132 of the PALB2 protein (p.Val132Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. |
Ambry Genetics | RCV003365621 | SCV004057642 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-22 | criteria provided, single submitter | clinical testing | The p.V132I variant (also known as c.394G>A), located in coding exon 4 of the PALB2 gene, results from a G to A substitution at nucleotide position 394. The valine at codon 132 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |