ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.7900C>T (p.Pro2634Ser) (rs587781791)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234554 SCV000284520 uncertain significance Neurofibromatosis, type 1 2019-06-09 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2634 of the NF1 protein (p.Pro2634Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. 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: 237601). Algorithms developed to predict the effect of missense changes on protein structure and function 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.
Ambry Genetics RCV000569910 SCV000662764 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-25 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
PreventionGenetics,PreventionGenetics RCV000679417 SCV000806323 uncertain significance not provided 2017-08-11 criteria provided, single submitter clinical testing
GeneDx RCV000679417 SCV000808551 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing This variant is denoted NF1 c.7900C>T at the cDNA level, p.Pro2634Ser (P2634S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Pro2634Ser was not observed in large population cohorts (Lek 2016). This variant is located in the C-terminal domain . In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect (Luo 2014). Based on currently available evidence, it is unclear whether NF1 Pro2634Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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