ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.8087C>T (p.Pro2696Leu) (rs778799019)

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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 RCV000572639 SCV000663113 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
GeneDx RCV000681184 SCV000808642 uncertain significance not provided 2018-03-29 criteria provided, single submitter clinical testing The P2696L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is observed in 3/33532 (0.0089%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). P2696L is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000804420 SCV000944331 uncertain significance Neurofibromatosis, type 1 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2696 of the NF1 protein (p.Pro2696Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs778799019, ExAC 0.009%). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 480106). 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: "Deleterious"; 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.

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