ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.1192G>A (p.Val398Met)

gnomAD frequency: 0.00001  dbSNP: rs769097541
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553689 SCV000633266 uncertain significance Familial cancer of breast 2023-04-08 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 460885). This missense change has been observed in individual(s) with breast cancer (PMID: 28825143, 30287823). This variant is present in population databases (rs769097541, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 398 of the PALB2 protein (p.Val398Met).
Color Diagnostics, LLC DBA Color Health RCV000771520 SCV000904034 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000771520 SCV001170323 likely benign Hereditary cancer-predisposing syndrome 2018-04-23 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Leiden Open Variation Database RCV001030202 SCV001193070 uncertain significance not provided 2018-10-10 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.

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