ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.3325T>C (p.Cys1109Arg)

dbSNP: rs911734555
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000470766 SCV000550766 uncertain significance Familial cancer of breast 2023-12-25 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1109 of the PALB2 protein (p.Cys1109Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 410196). 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 RCV000568208 SCV000666896 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-11 criteria provided, single submitter clinical testing The p.C1109R variant (also known as c.3325T>C), located in coding exon 12 of the PALB2 gene, results from a T to C substitution at nucleotide position 3325. The cysteine at codon 1109 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is 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.
Color Diagnostics, LLC DBA Color Health RCV000568208 SCV001348508 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-14 criteria provided, single submitter clinical testing This missense variant replaces cysteine with arginine at codon 1109 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Sema4, Sema4 RCV000568208 SCV002531170 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-18 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002496778 SCV002788141 uncertain significance Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 2022-04-19 criteria provided, single submitter clinical testing
Baylor Genetics RCV000470766 SCV005053895 uncertain significance Familial cancer of breast 2024-02-10 criteria provided, single submitter clinical testing

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