NM_001007792.1(NTRK1):c.500A>G (p.Lys167Arg) AND Hereditary insensitivity to pain with anhidrosis

Clinical significance:Uncertain significance (Last evaluated: Jan 26, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001071741.3

Allele description [Variation Report for NM_001007792.1(NTRK1):c.500A>G (p.Lys167Arg)]

NM_001007792.1(NTRK1):c.500A>G (p.Lys167Arg)

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.500A>G (p.Lys167Arg)
HGVS:
  • NC_000001.11:g.156868520A>G
  • NG_007493.1:g.57771A>G
  • NM_001007792.1:c.500A>G
  • NM_001012331.1:c.590A>G
  • NM_002529.3:c.590A>G
  • NP_001007793.1:p.Lys167Arg
  • NP_001012331.1:p.Lys197Arg
  • NP_002520.2:p.Lys197Arg
  • LRG_261t1:c.500A>G
  • LRG_261t2:c.590A>G
  • LRG_261t3:c.590A>G
  • LRG_261:g.57771A>G
  • LRG_261p1:p.Lys167Arg
  • LRG_261p2:p.Lys197Arg
  • LRG_261p3:p.Lys197Arg
  • NC_000001.10:g.156838312A>G
Protein change:
K167R
Molecular consequence:
  • NM_001007792.1:c.500A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001012331.1:c.590A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002529.3:c.590A>G - 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
SCV001237061Invitaecriteria provided, single submitter
Uncertain significance
(Jan 26, 2019)
germlineclinical testing

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

SCV001459282Natera, Inc.no assertion criteria providedUncertain significance
(Apr 17, 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, SCV001237061.2

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

Description

This sequence change replaces lysine with arginine at codon 197 of the NTRK1 protein (p.Lys197Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with NTRK1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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., SCV001459282.1

#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