ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.512A>G (p.Asn171Ser) (rs767500770)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166685 SCV000217493 uncertain significance Hereditary cancer-predisposing syndrome 2014-11-13 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 RCV000681197 SCV000808655 uncertain significance not provided 2018-04-04 criteria provided, single submitter clinical testing This variant is denoted NF1 c.512A>G at the cDNA level, p.Asn171Ser (N171S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Asn171Ser was not observed at a significant allele frequency 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 a deleterious effect. Based on currently available evidence, it is unclear whether NF1 Asn171Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000234201 SCV000284474 uncertain significance Neurofibromatosis, type 1 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 171 of the NF1 protein (p.Asn171Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs767500770, ExAC 0.003%). This variant has not been reported in the literature in individuals with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 187007). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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