ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.3377A>C (p.His1126Pro)

dbSNP: rs752373316
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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 RCV000217197 SCV000273224 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-29 criteria provided, single submitter clinical testing The p.H1126P variant (also known as c.3377A>C), located in coding exon 13 of the PALB2 gene, results from an A to C substitution at nucleotide position 3377. The histidine at codon 1126 is replaced by proline, an amino acid with similar properties. This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000469669 SCV000550617 uncertain significance Familial cancer of breast 2022-08-04 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is present in population databases (rs752373316, gnomAD 0.009%). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1126 of the PALB2 protein (p.His1126Pro). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 229867).
Color Diagnostics, LLC DBA Color Health RCV000217197 SCV001354179 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces histidine with proline at codon 1126 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 3/251428 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.
Baylor Genetics RCV000469669 SCV005053943 uncertain significance Familial cancer of breast 2023-12-12 criteria provided, single submitter clinical testing

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