NM_002529.4(NTRK1):c.1649_1650insGGCAGGAAGTCGGCACTGAA (p.Glu551_Ser552insAlaGlySerArgHisTer) AND Hereditary insensitivity to pain with anhidrosis

Clinical significance:Pathogenic (Last evaluated: Mar 17, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001387630.1

Allele description [Variation Report for NM_002529.4(NTRK1):c.1649_1650insGGCAGGAAGTCGGCACTGAA (p.Glu551_Ser552insAlaGlySerArgHisTer)]

NM_002529.4(NTRK1):c.1649_1650insGGCAGGAAGTCGGCACTGAA (p.Glu551_Ser552insAlaGlySerArgHisTer)

Gene:
NTRK1:neurotrophic receptor tyrosine kinase 1 [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
1q23.1
Genomic location:
Preferred name:
NM_002529.4(NTRK1):c.1649_1650insGGCAGGAAGTCGGCACTGAA (p.Glu551_Ser552insAlaGlySerArgHisTer)
HGVS:
  • NC_000001.11:g.156876416_156876417insGGCAGGAAGTCGGCACTGAA
  • NG_007493.1:g.65667_65668insGGCAGGAAGTCGGCACTGAA
  • NM_001007792.1:c.1541_1542insGGCAGGAAGTCGGCACTGAA
  • NM_001012331.2:c.1631_1632insGGCAGGAAGTCGGCACTGAA
  • NM_002529.4:c.1649_1650insGGCAGGAAGTCGGCACTGAAMANE SELECT
  • NP_001007793.1:p.Glu515_Ser516insAlaGlySerArgHisTer
  • NP_001012331.1:p.Glu545_Ser546insAlaGlySerArgHisTer
  • NP_002520.2:p.Glu551_Ser552insAlaGlySerArgHisTer
  • LRG_261t1:c.1541_1542insGGCAGGAAGTCGGCACTGAA
  • LRG_261:g.65667_65668insGGCAGGAAGTCGGCACTGAA
  • LRG_261p1:p.Glu515_Ser516insAlaGlySerArgHisTer
  • NC_000001.10:g.156846208_156846209insGGCAGGAAGTCGGCACTGAA
Molecular consequence:
  • NM_001007792.1:c.1541_1542insGGCAGGAAGTCGGCACTGAA - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001012331.2:c.1631_1632insGGCAGGAAGTCGGCACTGAA - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_002529.4:c.1649_1650insGGCAGGAAGTCGGCACTGAA - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001007792.1:c.1541_1542insGGCAGGAAGTCGGCACTGAA - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001012331.2:c.1631_1632insGGCAGGAAGTCGGCACTGAA - nonsense - [Sequence Ontology: SO:0001587]
  • NM_002529.4:c.1649_1650insGGCAGGAAGTCGGCACTGAA - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Hereditary insensitivity to pain with anhidrosis (CIPA)
Synonyms:
FAMILIAL DYSAUTONOMIA, TYPE II; Insensitivity to pain, congenital, with anhidrosis; Neuropathy, congenital sensory, with anhidrosis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009746; MedGen: C0020074; Orphanet: 642; OMIM: 256800

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001588302Invitaecriteria provided, single submitter
Pathogenic
(Mar 17, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families.

Miura Y, Mardy S, Awaya Y, Nihei K, Endo F, Matsuda I, Indo Y.

Hum Genet. 2000 Jan;106(1):116-24. Erratum in: Hum Genet 2000 May;106(5):575.

PubMed [citation]
PMID:
10982191

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001588302.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Glu545Alafs*6) in the NTRK1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NTRK1-related conditions. Loss-of-function variants in NTRK1 are known to be pathogenic (PMID: 10982191). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 14, 2021

Support Center