NM_002529.4(NTRK1):c.65T>A (p.Leu22Gln) AND Hereditary insensitivity to pain with anhidrosis

Clinical significance:Uncertain significance (Last evaluated: Jun 14, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000525243.3

Allele description [Variation Report for NM_002529.4(NTRK1):c.65T>A (p.Leu22Gln)]

NM_002529.4(NTRK1):c.65T>A (p.Leu22Gln)

Gene:
NTRK1:neurotrophic receptor tyrosine kinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q23.1
Genomic location:
Preferred name:
NM_002529.4(NTRK1):c.65T>A (p.Leu22Gln)
HGVS:
  • NC_000001.11:g.156860999T>A
  • NG_007493.1:g.50250T>A
  • NM_001007792.1:c.123-3355T>A
  • NM_001012331.1:c.65T>A
  • NM_001012331.2:c.65T>A
  • NM_002529.4:c.65T>AMANE SELECT
  • NP_001012331.1:p.Leu22Gln
  • NP_001012331.1:p.Leu22Gln
  • NP_002520.2:p.Leu22Gln
  • LRG_261t1:c.123-3355T>A
  • LRG_261t2:c.65T>A
  • LRG_261:g.50250T>A
  • LRG_261p2:p.Leu22Gln
  • NC_000001.10:g.156830791T>A
Protein change:
L22Q
Links:
dbSNP: rs748402400
NCBI 1000 Genomes Browser:
rs748402400
Molecular consequence:
  • NM_001007792.1:c.123-3355T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001012331.1:c.65T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001012331.2:c.65T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002529.4:c.65T>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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000626976Invitaecriteria provided, single submitter
Uncertain significance
(Jun 14, 2019)
germlineclinical testing

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

SCV001455163Natera, 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, SCV000626976.2

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

Description

This sequence change replaces leucine with glutamine at codon 22 of the NTRK1 protein (p.Leu22Gln). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and glutamine. This variant is present in population databases (rs748402400, ExAC 0.1%). 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 C0"). 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., SCV001455163.1

#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: Oct 25, 2021

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