Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001191748 | SCV001359647 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-07 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 50 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001859154 | SCV002297073 | uncertain significance | Familial cancer of breast | 2021-10-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 928094). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This sequence change replaces lysine with glutamic acid at codon 50 of the PALB2 protein (p.Lys50Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. |