ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.1052C>A (p.Thr351Lys)

gnomAD frequency: 0.00001  dbSNP: rs876658656
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218423 SCV000274189 likely benign Hereditary cancer-predisposing syndrome 2024-03-27 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000531194 SCV000633247 uncertain significance Familial cancer of breast 2022-05-27 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 230592). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 351 of the PALB2 protein (p.Thr351Lys).
Color Diagnostics, LLC DBA Color Health RCV000218423 SCV002051895 uncertain significance Hereditary cancer-predisposing syndrome 2021-03-16 criteria provided, single submitter clinical testing This missense variant replaces threonine with lysine at codon 351 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics RCV000531194 SCV004202079 uncertain significance Familial cancer of breast 2023-09-14 criteria provided, single submitter clinical testing

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