ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.1861C>T (p.Pro621Ser)

dbSNP: rs756116550
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002041332 SCV002110478 uncertain significance Familial cancer of breast 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 621 of the PALB2 protein (p.Pro621Ser). 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: 1346049). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PALB2 protein function with a negative predictive value of 80%. 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 RCV002406911 SCV002724105 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-23 criteria provided, single submitter clinical testing The p.P621S variant (also known as c.1861C>T), located in coding exon 5 of the PALB2 gene, results from a C to T substitution at nucleotide position 1861. The proline at codon 621 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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 RCV003234121 SCV003931090 uncertain significance not provided 2022-12-06 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: 22941656)

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