ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.887T>G (p.Met296Arg)

dbSNP: rs1555461566
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000534516 SCV000633485 uncertain significance Familial cancer of breast 2020-02-07 criteria provided, single submitter clinical testing In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PALB2-related disease. This sequence change replaces methionine with arginine at codon 296 of the PALB2 protein (p.Met296Arg). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and arginine.
Ambry Genetics RCV002377044 SCV002684540 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-30 criteria provided, single submitter clinical testing The p.M296R variant (also known as c.887T>G), located in coding exon 4 of the PALB2 gene, results from a T to G substitution at nucleotide position 887. The methionine at codon 296 is replaced by arginine, an amino acid with similar properties. This amino acid position is poorly 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.
GeneDx RCV004767346 SCV005379809 uncertain significance not provided 2023-11-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 19369211)

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