ClinVar Miner

Submissions for variant NM_001007792.1(NTRK1):c.775C>A (p.Gln259Lys) (rs137979116)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236758 SCV000292639 uncertain significance not provided 2018-04-16 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NTRK1 gene. The Q289K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. Q289K is listed in the NTRK1 LOVD database as a variant of unknown significance and no additional information is provided. The Q289K variant is observed in 230/122508 (0.2%) alleles from individuals of non-Finnish European background (Lek et al., 2016). The Q289K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether the Q289K variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000284934 SCV000349048 uncertain significance Hereditary insensitivity to pain with anhidrosis 2018-01-12 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.
Invitae RCV000284934 SCV000626979 likely benign Hereditary insensitivity to pain with anhidrosis 2020-12-06 criteria provided, single submitter clinical testing
Mendelics RCV000708813 SCV000837799 uncertain significance Familial medullary thyroid carcinoma 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000284934 SCV001135444 uncertain significance Hereditary insensitivity to pain with anhidrosis 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000284934 SCV001472839 uncertain significance Hereditary insensitivity to pain with anhidrosis 2020-04-17 criteria provided, single submitter clinical testing The NTRK1 c.865C>A; p.Gln289Lys variant (rs137979116), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 245652). This variant is found in the non-Finnish European population with an allele frequency of 0.2% (227/124,316 alleles) in the Genome Aggregation Database. The glutamine at codon 289 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, given the lack of clinical and functional data, the significance of the p.Gln289Lys variant is uncertain at this time.
Natera, Inc. RCV000284934 SCV001459288 likely benign Hereditary insensitivity to pain with anhidrosis 2020-04-17 no assertion criteria provided clinical testing

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