ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2921A>G (p.Asn974Ser) (rs557875547)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165243 SCV000215958 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbSNP, ESP, 1000 Genomes),Insufficient or Conflicting Evidence,in silico models in agreement (benign)
GeneDx RCV000681074 SCV000808528 uncertain significance not provided 2017-12-22 criteria provided, single submitter clinical testing This variant is denoted NF1 c.2921A>G at the cDNA level, p.Asn974Ser (N974S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant was observed in the germline of an individual with mesothelioma (Yoshikawa 2015), and has also been reported as a somatic variant in a liposarcoma and pheochromocytoma (Asano 2017, Pillai 2017). NF1 Asn974Ser was observed at an allele frequency of 0.1% (37/30,782) in individuals of South Asian ancestry in large population cohorts (Lek 2016). NF1 Asn974Ser is located within the GTPase activating protein domain (Xu 1990, Luo 2014). 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 NF1 Asn974Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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