ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.137A>G (p.His46Arg)

gnomAD frequency: 0.00001  dbSNP: rs1290624507
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000635748 SCV000757170 uncertain significance Familial cancer of breast 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 46 of the PALB2 protein (p.His46Arg). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 530102). 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 tolerated. 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 RCV001011256 SCV001171555 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-29 criteria provided, single submitter clinical testing The p.H46R variant (also known as c.137A>G), located in coding exon 3 of the PALB2 gene, results from an A to G substitution at nucleotide position 137. The histidine at codon 46 is replaced by arginine, an amino acid with highly 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 RCV001527324 SCV001738292 uncertain significance not provided 2020-01-24 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016) In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV000635748 SCV004202133 uncertain significance Familial cancer of breast 2023-08-13 criteria provided, single submitter clinical testing

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