ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.389A>G (p.His130Arg) (rs876660277)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000525286 SCV000628555 uncertain significance Neurofibromatosis, type 1 2019-12-01 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 130 of the NF1 protein (p.His130Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 457673). 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.
Ambry Genetics RCV000563492 SCV000670456 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-20 criteria provided, single submitter clinical testing Insufficient evidence
Johns Hopkins Genomics,Johns Hopkins University RCV000525286 SCV001425358 uncertain significance Neurofibromatosis, type 1 2020-03-31 criteria provided, single submitter clinical testing This NF1 variant is absent from a large population dataset and has not been reported in the literature, to our knowledge. Two submitters in ClinVar classify c.389A>G as a variant of uncertain clinical significance. Three bioinformatic tools queried predict that this substitution would be tolerated, and the histidine residue at this position is highly evolutionarily conserved across most species assessed. Due to insufficient evidence, we consider the clinical significance of c.389A>G to be uncertain at this time.

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