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NM_001012331.1(NTRK1):c.2028+3A>C AND Hereditary insensitivity to pain with anhidrosis

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 13, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000706507.1

Allele description

NM_001012331.1(NTRK1):c.2028+3A>C

Gene:
NTRK1:neurotrophic receptor tyrosine kinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q23.1
Genomic location:
Preferred name:
NM_001012331.1(NTRK1):c.2028+3A>C
HGVS:
  • NC_000001.11:g.156879365A>C
  • NG_007493.1:g.68616A>C
  • NM_001007792.1:c.1938+3A>C
  • NM_001012331.1:c.2028+3A>C
  • NM_002529.3:c.2046+3A>C
  • LRG_261t1:c.1938+3A>C
  • LRG_261t2:c.2028+3A>C
  • LRG_261t3:c.2046+3A>C
  • LRG_261:g.68616A>C
  • NC_000001.10:g.156849157A>C
Links:
dbSNP: rs914061514
NCBI 1000 Genomes Browser:
rs914061514
Molecular consequence:
  • NM_001012331.1:c.2028+3A>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Hereditary insensitivity to pain with anhidrosis (CIPA)
Synonyms:
FAMILIAL DYSAUTONOMIA, TYPE II; HSAN Type IV; Hereditary Sensory and Autonomic Neuropathy Type IV
Identifiers:
MedGen: C0020074; Orphanet: 642; OMIM: 256800

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000835562Invitae
criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))		Likely pathogenic
(Mar 13, 2018) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis.

Indo Y, Tsuruta M, Hayashida Y, Karim MA, Ohta K, Kawano T, Mitsubuchi H, Tonoki H, Awaya Y, Matsuda I.

Nat Genet. 1996 Aug;13(4):485-8.

PubMed [citation]
PMID:
8696348

Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.

Rotthier A, Baets J, De Vriendt E, Jacobs A, Auer-Grumbach M, Lévy N, Bonello-Palot N, Kilic SS, Weis J, Nascimento A, Swinkels M, Kruyt MC, Jordanova A, De Jonghe P, Timmerman V.

Brain. 2009 Oct;132(Pt 10):2699-711. doi: 10.1093/brain/awp198. Epub 2009 Aug 3.

PubMed [citation]
PMID:
19651702
PMCID:
PMC2759337
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000835562.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change falls in intron 14 of the NTRK1 gene. It does not directly change the encoded amino acid sequence of the NTRK1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with disease in a family affected with congenital insensitivity to pain with anhidrosis (PMID: 8696348). It has also been reported in an individual with sensory and autonomic neuropathies (PMID: 19651702). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this splice variant causes aberrant splicing and a partial exon deletion (PMID: 8696348). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 13, 2018