ClinVar Miner

Submissions for variant NM_002529.4(NTRK1):c.1808C>G (p.Ser603Cys)

gnomAD frequency: 0.00011  dbSNP: rs188270548
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000366642 SCV000349058 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.
Eurofins Ntd Llc (ga) RCV000591215 SCV000701876 uncertain significance not provided 2016-10-04 criteria provided, single submitter clinical testing
Mendelics RCV000708821 SCV000837807 uncertain significance Familial medullary thyroid carcinoma 2018-07-02 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000591215 SCV001748173 uncertain significance not provided 2022-11-01 criteria provided, single submitter clinical testing NTRK1: PM2, PP3
Ambry Genetics RCV002411184 SCV002717205 uncertain significance Inborn genetic diseases 2022-03-22 criteria provided, single submitter clinical testing The p.S597C variant (also known as c.1790C>G), located in coding exon 14 of the NTRK1 gene, results from a C to G substitution at nucleotide position 1790. The serine at codon 597 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000366642 SCV002945203 uncertain significance Hereditary insensitivity to pain with anhidrosis 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 597 of the NTRK1 protein (p.Ser597Cys). This variant is present in population databases (rs188270548, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NTRK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 292892). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV000366642 SCV003814194 uncertain significance Hereditary insensitivity to pain with anhidrosis 2020-09-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000366642 SCV004048751 uncertain significance Hereditary insensitivity to pain with anhidrosis 2023-04-11 criteria provided, single submitter clinical testing
3billion RCV000366642 SCV005328886 likely benign Hereditary insensitivity to pain with anhidrosis 2024-09-20 criteria provided, single submitter clinical testing The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.
Natera, Inc. RCV000366642 SCV001467154 uncertain significance Hereditary insensitivity to pain with anhidrosis 2020-04-17 no assertion criteria provided clinical testing

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