Submissions for variant NM_002529.4(NTRK1):c.570C>G (p.Ser190Arg)

gnomAD frequency: 0.00013  dbSNP: rs138608619

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000291812	SCV000349042	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000291812	SCV000752382	likely benign	Hereditary insensitivity to pain with anhidrosis	2024-01-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000708810	SCV000837796	uncertain significance	Familial medullary thyroid carcinoma	2018-07-02	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001509068	SCV001715580	uncertain significance	not provided	2020-09-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002348032	SCV002649596	likely benign	Inborn genetic diseases	2020-07-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001509068	SCV005396453	uncertain significance	not provided	2024-05-08	criteria provided, single submitter	clinical testing	Reported previously as a variant of uncertain significance in a patient with congenital insensitivity to pain and anhidrosis who harbored numerous other variants in NTRK1 and other genes, including some that were pathogenic (PMID: 32807182); In silico analysis supports a deleterious effect on splicing; In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34160418, 32807182)
PreventionGenetics, part of Exact Sciences	RCV003897665	SCV004712940	likely benign	NTRK1-related disorder	2020-09-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).