ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.3317T>C (p.Met1106Thr)

gnomAD frequency: 0.00001  dbSNP: rs769065406
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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 RCV000538048 SCV000633422 uncertain significance Familial cancer of breast 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1106 of the PALB2 protein (p.Met1106Thr). This variant is present in population databases (rs769065406, 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: 460989). 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 tolerated. 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.
Color Diagnostics, LLC DBA Color Health RCV001190818 SCV001358406 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces methionine with threonine at codon 1106 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 1/251480 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.
GeneDx RCV001541422 SCV001759419 uncertain significance not provided 2019-09-18 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Ambry Genetics RCV001190818 SCV002606194 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-24 criteria provided, single submitter clinical testing The p.M1106T variant (also known as c.3317T>C), located in coding exon 12 of the PALB2 gene, results from a T to C substitution at nucleotide position 3317. The methionine at codon 1106 is replaced by threonine, an amino acid with similar 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.
Baylor Genetics RCV000538048 SCV005053869 uncertain significance Familial cancer of breast 2024-03-08 criteria provided, single submitter clinical testing

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