ClinVar Miner

Submissions for variant NM_002529.3(NTRK1):c.2303C>T (p.Pro768Leu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Inherited Neuropathy Consortium RCV000789685 SCV000929060 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Invitae RCV000820283 SCV000960990 pathogenic Hereditary insensitivity to pain with anhidrosis 2018-11-28 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 762 of the NTRK1 protein (p.Pro762Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs756981419, ExAC 0.04%). This variant has been observed in individuals with sensory and autonomic neuropathy type IV (PMID: 15534759, 22032467, 23112235). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

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