ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.947C>T (p.Pro316Leu)

dbSNP: rs876658867
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221523 SCV000274665 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-25 criteria provided, single submitter clinical testing The p.P316L variant (also known as c.947C>T), located in coding exon 4 of the PALB2 gene, results from a C to T substitution at nucleotide position 947. The proline at codon 316 is replaced by leucine, an amino acid with similar properties. Based on protein sequence alignment, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000687299 SCV000814858 uncertain significance Familial cancer of breast 2021-03-01 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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 not been reported in the literature in individuals with PALB2-related disease. ClinVar contains an entry for this variant (Variation ID: 230958). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 316 of the PALB2 protein (p.Pro316Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine.
Sema4, Sema4 RCV000221523 SCV002531237 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-17 criteria provided, single submitter curation
Baylor Genetics RCV000687299 SCV004202100 uncertain significance Familial cancer of breast 2023-09-04 criteria provided, single submitter clinical testing

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