NM_001007792.1(NTRK1):c.1417G>A (p.Asp473Asn) AND Hereditary insensitivity to pain with anhidrosis

Clinical significance:Uncertain significance (Last evaluated: Oct 26, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000631331.2

Allele description [Variation Report for NM_001007792.1(NTRK1):c.1417G>A (p.Asp473Asn)]

NM_001007792.1(NTRK1):c.1417G>A (p.Asp473Asn)

Gene:
NTRK1:neurotrophic receptor tyrosine kinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q23.1
Genomic location:
Preferred name:
NM_001007792.1(NTRK1):c.1417G>A (p.Asp473Asn)
HGVS:
  • NC_000001.11:g.156876103G>A
  • NG_007493.1:g.65354G>A
  • NM_001007792.1:c.1417G>A
  • NM_001012331.1:c.1507G>A
  • NM_002529.3:c.1525G>A
  • NP_001007793.1:p.Asp473Asn
  • NP_001012331.1:p.Asp503Asn
  • NP_002520.2:p.Asp509Asn
  • LRG_261t1:c.1417G>A
  • LRG_261t2:c.1507G>A
  • LRG_261t3:c.1525G>A
  • LRG_261:g.65354G>A
  • LRG_261p1:p.Asp473Asn
  • LRG_261p2:p.Asp503Asn
  • LRG_261p3:p.Asp509Asn
  • NC_000001.10:g.156845895G>A
Protein change:
D473N
Links:
dbSNP: rs1035934237
NCBI 1000 Genomes Browser:
rs1035934237
Molecular consequence:
  • NM_001007792.1:c.1417G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001012331.1:c.1507G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002529.3:c.1525G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000752361Invitaecriteria provided, single submitter
Uncertain significance
(Oct 26, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001467150Natera, Inc.no assertion criteria providedUncertain significance
(Sep 30, 2020)
germlineclinical testing

Summary from all submissions

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

Citations

PubMed

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, SCV000752361.1

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

Description

This sequence change replaces aspartic acid with asparagine at codon 503 of the NTRK1 protein (p.Asp503Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. 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 disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Natera, Inc., SCV001467150.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 27, 2021

Support Center