ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.1340C>A (p.Ala447Glu)

dbSNP: rs1555461334
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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 RCV000570239 SCV000663407 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-30 criteria provided, single submitter clinical testing The p.A447E variant (also known as c.1340C>A), located in coding exon 4 of the PALB2 gene, results from a C to A substitution at nucleotide position 1340. The alanine at codon 447 is replaced by glutamic acid, an amino acid with dissimilar properties. 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 RCV000635800 SCV000757223 uncertain significance Familial cancer of breast 2024-11-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 447 of the PALB2 protein (p.Ala447Glu). 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: 480285). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Fulgent Genetics, Fulgent Genetics RCV000765275 SCV000896528 uncertain significance Familial cancer of breast; Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3 2018-10-31 criteria provided, single submitter clinical testing

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