ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.1348A>C (p.Asn450His) (rs62625274)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212791 SCV000149976 uncertain significance not provided 2018-04-13 criteria provided, single submitter clinical testing This variant is denoted PALB2 c.1348A>C at the cDNA level, p.Asn450His (N450H) at the protein level, and results in the change of an Asparagine to a Histidine (AAT>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PALB2 Asn450His was not observed in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether PALB2 Asn450His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000116067 SCV000216351 uncertain significance Hereditary cancer-predisposing syndrome 2014-09-02 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000198442 SCV000255077 uncertain significance Familial cancer of breast 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 450 of the PALB2 protein (p.Asn450His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 128119). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000116067 SCV000685875 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-08 criteria provided, single submitter clinical testing
Counsyl RCV000198442 SCV000785652 uncertain significance Familial cancer of breast 2017-10-19 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765274 SCV000896527 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group N; Pancreatic cancer 3 2018-10-31 criteria provided, single submitter clinical testing

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