Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000579885 | SCV000686015 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-16 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with glutamic acid at codon 1068 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 reported in two individuals affected with breast cancer (PMID: 28779002) and an individual affected with unspecified cancer (PMID: 28873162), and this variant has been detected in a breast cancer case-control meta-analysis in 2/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID PALB2_010771). This variant has been identified in 1/251408 chromosomes 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. |
| Labcorp Genetics |
RCV000635679 | SCV000757100 | uncertain significance | Familial cancer of breast | 2023-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1068 of the PALB2 protein (p.Gly1068Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 28779002, 30638972). ClinVar contains an entry for this variant (Variation ID: 490082). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Ambry Genetics | RCV000579885 | SCV001180533 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-27 | criteria provided, single submitter | clinical testing | The p.G1068E variant (also known as c.3203G>A), located in coding exon 12 of the PALB2 gene, results from a G to A substitution at nucleotide position 3203. The glycine at codon 1068 is replaced by glutamic acid, an amino acid with similar properties. This alteration has been reported in 2/13087 breast cancer cases and 0/5488 control individuals in the UK (Decker B et al. J. Med. Genet., 2017 Nov;54:732-741). In another study, this variant was reported in 2/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Sema4, |
RCV000579885 | SCV002530761 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-27 | criteria provided, single submitter | curation | |
| Baylor Genetics | RCV000635679 | SCV004202165 | uncertain significance | Familial cancer of breast | 2023-07-19 | criteria provided, single submitter | clinical testing |