ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.1643C>T (p.Ser548Leu)

dbSNP: rs1241049372
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547156 SCV000633294 uncertain significance Familial cancer of breast 2022-08-05 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with PALB2-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 460904). This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 548 of the PALB2 protein (p.Ser548Leu).
Ambry Genetics RCV000571222 SCV000665308 likely benign Hereditary cancer-predisposing syndrome 2016-08-04 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.
GeneDx RCV002259347 SCV002538868 uncertain significance not provided 2021-12-27 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

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