ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.406A>T (p.Ser136Cys)

gnomAD frequency: 0.00001  dbSNP: rs144496685
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000542390 SCV000633448 uncertain significance Familial cancer of breast 2023-09-20 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 136 of the PALB2 protein (p.Ser136Cys). This variant is present in population databases (rs144496685, gnomAD 0.007%). 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: 461001). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics RCV001021800 SCV001183461 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.
Baylor Genetics RCV000542390 SCV004202088 uncertain significance Familial cancer of breast 2024-01-08 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001021800 SCV004357986 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-13 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 136 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 PALB2-related disorders in the literature. This variant has been identified in 2/251168 chromosomes 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004525963 SCV005039933 uncertain significance not specified 2024-03-09 criteria provided, single submitter clinical testing

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