ClinVar Miner

Submissions for variant NM_001007792.1(NTRK1):c.123-3404C>T (rs201472270)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000220958 SCV000279129 likely benign not specified 2018-01-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000299635 SCV000349034 uncertain significance Hereditary insensitivity to pain with anhidrosis 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000220958 SCV000604570 uncertain significance not specified 2018-07-23 criteria provided, single submitter clinical testing The NTRK1 c.16C>T; p.Arg6Trp variant (rs201472270) is reported in the literature in at least one individual with an inherited neuropathy; however, this variant was not thought to contribute to disease (Davidson 2012). This variant is reported as uncertain significance/likely benign by multiple laboratories in ClinVar (Variation ID: 234386), and is found in the general population with an overall allele frequency of 0.33% (411/123528 alleles) in the Genome Aggregation Database. The arginine at codon 6 is highly conserved, but computational analyses (SIFT: damaging, PolyPhen-2:benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the c.16C>T; p.Arg6Trp variant is uncertain at this time. Gene specific statement: Pathogenic variants in NTRK1 are associated with autosomal recessive congenital insensitivity to pain with anhidrosis (MIM: 256800) and autosomal dominant familial medullary thyroid carcinoma (MIM: 155240). References: Davidson et al. Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort. J Neurol. 2012 Aug;259(8):1673-85.
Invitae RCV000299635 SCV000626947 likely benign Hereditary insensitivity to pain with anhidrosis 2020-12-08 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000299635 SCV000803490 likely benign Hereditary insensitivity to pain with anhidrosis 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Benign, for Insensitivity to pain, congenital, with anhidrosis, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP5 =>Variant found in a case with an alternate molecular basis for disease (PMID:22302274). BS1-Supporting => BS1 downgraded in strength to supporting.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000220958 SCV000856552 benign not specified 2017-09-13 criteria provided, single submitter clinical testing
Mendelics RCV000299635 SCV001135439 likely benign Hereditary insensitivity to pain with anhidrosis 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000755590 SCV001147473 likely benign not provided 2020-12-01 criteria provided, single submitter clinical testing
Natera, Inc. RCV000299635 SCV001455162 uncertain significance Hereditary insensitivity to pain with anhidrosis 2020-01-06 no assertion criteria provided clinical testing

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