ClinVar Genomic variation as it relates to human health
NM_002529.4(NTRK1):c.1810C>T (p.His604Tyr)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002529.4(NTRK1):c.1810C>T (p.His604Tyr)
Variation ID: 37077 Accession: VCV000037077.45
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q23.1 1: 156879126 (GRCh38) [ NCBI UCSC ] 1: 156848918 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Sep 29, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002529.4:c.1810C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002520.2:p.His604Tyr missense NM_001007792.1:c.1702C>T NP_001007793.1:p.His568Tyr missense NM_001012331.2:c.1792C>T NP_001012331.1:p.His598Tyr missense NC_000001.11:g.156879126C>T NC_000001.10:g.156848918C>T NG_007493.1:g.68377C>T LRG_261:g.68377C>T LRG_261t1:c.1702C>T LRG_261p1:p.His568Tyr LRG_261t2:c.1792C>T LRG_261p2:p.His598Tyr LRG_261t3:c.1810C>T LRG_261p3:p.His604Tyr P04629:p.His604Tyr - Protein change
- H598Y, H568Y, H604Y
- Other names
- -
- Canonical SPDI
- NC_000001.11:156879125:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.02436 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.02436
1000 Genomes Project 30x 0.02436
Trans-Omics for Precision Medicine (TOPMed) 0.03655
The Genome Aggregation Database (gnomAD) 0.03696
The Genome Aggregation Database (gnomAD), exomes 0.04165
Exome Aggregation Consortium (ExAC) 0.04253
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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NTRK1 | - | - |
GRCh38 GRCh37 |
1338 | 1523 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
no assertion criteria provided
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Aug 1, 1999 | RCV000013100.25 | |
Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000030674.32 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Dec 10, 2021 | RCV000592514.13 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Oct 5, 2017 | RCV000712453.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Oct 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000842950.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
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Benign
(Mar 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000705487.2
First in ClinVar: Apr 02, 2018 Last updated: Apr 02, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary insensitivity to pain with anhidrosis
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000349059.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jul 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary insensitivity to pain with anhidrosis
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001748594.1
First in ClinVar: Jul 10, 2021 Last updated: Jul 10, 2021 |
Sex: mixed
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Benign
(Mar 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001856598.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 27884173, 10330344, 21228398, 20981092, 19435634, 11719521, 18780967, 11159935, 22995991, 20003389)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary insensitivity to pain with anhidrosis
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000626949.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
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Benign
(Nov 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary insensitivity to pain with anhidrosis
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001158856.8
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary insensitivity to pain with anhidrosis
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001135448.1
First in ClinVar: Jan 10, 2020 Last updated: Jan 10, 2020 |
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Likely benign
(Dec 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002050913.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Likely benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005262296.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Pathogenic
(Aug 01, 1999)
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no assertion criteria provided
Method: literature only
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THYROID CARCINOMA, FAMILIAL MEDULLARY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000033347.3
First in ClinVar: Apr 04, 2013 Last updated: May 17, 2019 |
Comment on evidence:
By SSCP analysis of 31 sporadic medullary thyroid carcinomas (155240), Gimm et al. (1999) detected variants in 5 exons (exons 4 and 14-17) of the … (more)
By SSCP analysis of 31 sporadic medullary thyroid carcinomas (155240), Gimm et al. (1999) detected variants in 5 exons (exons 4 and 14-17) of the NTRK1 gene. All variants were also present in the corresponding germline DNA. Interestingly, the sequence variants at codon 604 (C1810T/Y604H) and codon 613 (G1838T/V613G; 191315.0009) of exon 15 always occurred together, possibly representing linkage disequilibrium. (less)
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Benign
(Apr 17, 2020)
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no assertion criteria provided
Method: clinical testing
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Hereditary insensitivity to pain with anhidrosis
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001463407.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743876.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001924706.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927894.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001960072.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Hereditary insensitivity to pain with anhidrosis
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000040901.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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NTRK1 Congenital Insensitivity to Pain with Anhidrosis. | Adam MP | - | 2020 | PMID: 20301726 |
Novel pathogenic mechanisms of congenital insensitivity to pain with anhidrosis genetic disorder unveiled by functional analysis of neurotrophic tyrosine receptor kinase type 1/nerve growth factor receptor mutations. | Miranda C | The Journal of biological chemistry | 2002 | PMID: 11719521 |
Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor. | Mardy S | Human molecular genetics | 2001 | PMID: 11159935 |
Two novel mutant alleles of the gene encoding neurotrophic tyrosine kinase receptor type 1 (NTRK1) in a patient with congenital insensitivity to pain with anhidrosis: a splice junction mutation in intron 5 and cluster of four mutations in exon 15. | Bodzioch M | Human mutation | 2001 | PMID: 11139246 |
Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies. | Shatzky S | American journal of medical genetics | 2000 | PMID: 10861667 |
Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma. | Gimm O | The Journal of clinical endocrinology and metabolism | 1999 | PMID: 10443680 |
Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. | Mardy S | American journal of human genetics | 1999 | PMID: 10330344 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NTRK1 | - | - | - | - |
Text-mined citations for rs6336 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.