ClinVar Miner

Submissions for variant NM_002529.3(NTRK1):c.638T>C (p.Leu213Pro) (rs747711259)

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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 RCV000790288 SCV000929692 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Invitae RCV000631337 SCV000752368 pathogenic Hereditary insensitivity to pain with anhidrosis 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 213 of the NTRK1 protein (p.Leu213Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs747711259, ExAC 0.01%). This variant has been observed on the opposite chromosome (in trans) from other pathogenic variants in individuals affected with autosomal recessive congenital insensitivity to pain with anhidrosis (PMID: 10330344, 12949319). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Experimental studies have shown that this missense change produces an aberrantly processed NTRK1 protein that does not localize properly to the cell membrane and that does not retain tyrosine kinase activity (PMID: 11159935, 11719521, 27551041). For these reasons, this variant has been classified as Pathogenic.

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