Submissions for variant NM_002529.4(NTRK1):c.157G>C (p.Asp53His)

gnomAD frequency: 0.00187  dbSNP: rs200815412

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000356782	SCV000349035	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000356782	SCV000626946	benign	Hereditary insensitivity to pain with anhidrosis	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001532556	SCV001748170	likely benign	not provided	2021-04-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001532556	SCV001822552	uncertain significance	not provided	2024-08-20	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002402008	SCV002704160	likely benign	Inborn genetic diseases	2019-10-01	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.
Natera, Inc.	RCV000356782	SCV001459274	uncertain significance	Hereditary insensitivity to pain with anhidrosis	2020-04-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003957531	SCV004770428	likely benign	NTRK1-related disorder	2021-12-01	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).