ClinVar Miner

Submissions for variant NM_002529.4(NTRK1):c.2084C>T (p.Pro695Leu)

gnomAD frequency: 0.00001  dbSNP: rs121964868
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000013103 SCV000942069 pathogenic Hereditary insensitivity to pain with anhidrosis 2023-07-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 12310). This missense change has been observed in individuals with congenital insensitivity to pain with anhidrosis (PMID: 10861667, 30774415). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 689 of the NTRK1 protein (p.Pro689Leu).
Fulgent Genetics, Fulgent Genetics RCV000013103 SCV005678540 likely pathogenic Hereditary insensitivity to pain with anhidrosis 2024-03-23 criteria provided, single submitter clinical testing
OMIM RCV000013103 SCV000033350 pathogenic Hereditary insensitivity to pain with anhidrosis 2000-06-19 no assertion criteria provided literature only
Natera, Inc. RCV000013103 SCV002090072 likely pathogenic Hereditary insensitivity to pain with anhidrosis 2021-07-14 no assertion criteria provided clinical testing

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