Submissions for variant NM_002529.4(NTRK1):c.1287C>A (p.Cys429Ter)

dbSNP: rs1647805941

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001205093	SCV001376329	pathogenic	Hereditary insensitivity to pain with anhidrosis	2020-11-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Cys423*) in the NTRK1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NTRK1 are known to be pathogenic (PMID: 10982191). This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with NTRK1-related conditions.
Neuberg Centre For Genomic Medicine, NCGM	RCV001205093	SCV005061236	likely pathogenic	Hereditary insensitivity to pain with anhidrosis		criteria provided, single submitter	clinical testing	The stop gained c.1287C>A (p.Cys429Ter) variant in the NTRK1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is novel in the gnomAD Exomes and 1000 Genomes. It is submitted to ClinVar as Pathogenic. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense_x0002_mediated mRNA decay. Loss of function variants have been previously reported to be disease causing. Additional studies are required to prove the pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic