ClinVar Miner

Submissions for variant NM_002529.4(NTRK1):c.2303C>T (p.Pro768Leu)

gnomAD frequency: 0.00001  dbSNP: rs756981419
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000820283 SCV000960990 pathogenic Hereditary insensitivity to pain with anhidrosis 2023-12-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 762 of the NTRK1 protein (p.Pro762Leu). This variant is present in population databases (rs756981419, gnomAD 0.02%). This missense change has been observed in individual(s) with sensory and autonomic neuropathy type IV (PMID: 15534759, 22032467, 23112235). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.2303C>T (p.Pro768Leu). ClinVar contains an entry for this variant (Variation ID: 637485). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NTRK1 protein function. For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789685 SCV000929060 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences RCV000820283 SCV002549900 likely pathogenic Hereditary insensitivity to pain with anhidrosis 2021-11-16 no assertion criteria provided research

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