Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000198123 | SCV000255105 | uncertain significance | Familial cancer of breast | 2022-03-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1150 of the PALB2 protein (p.Leu1150Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 26283626). ClinVar contains an entry for this variant (Variation ID: 216755). 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 C0"). 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. |
Cancer Genetics Laboratory, |
RCV000198123 | SCV000268029 | uncertain significance | Familial cancer of breast | 2015-06-01 | criteria provided, single submitter | case-control | |
Color Diagnostics, |
RCV000776376 | SCV000911814 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-18 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 1150 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 been detected in two breast cancer case-control studies in one affected individual and absent in unaffected control individuals, and in the largest of the two study it was found in 1/60466 cases and 0/53461 unaffected individuals (PMID: 26283626, 33471991; Leiden Open Variation Database DB-ID PALB2_010744). 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284322 | SCV001470044 | uncertain significance | not provided | 2020-05-25 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000776376 | SCV002531180 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-28 | criteria provided, single submitter | curation |