ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.1189A>C (p.Thr397Pro)

dbSNP: rs367578415
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001010230 SCV001170393 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-20 criteria provided, single submitter clinical testing The p.T397P variant (also known as c.1189A>C), located in coding exon 4 of the PALB2 gene, results from an A to C substitution at nucleotide position 1189. The threonine at codon 397 is replaced by proline, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002497334 SCV002777393 uncertain significance Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 2021-09-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003769426 SCV004668555 uncertain significance Familial cancer of breast 2022-11-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 397 of the PALB2 protein (p.Thr397Pro). 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: 818541). 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 expected to disrupt PALB2 protein function. 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.

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