U.S. flag

An official website of the United States government

NM_001007792.1(NTRK1):c.163C>A (p.Arg55Ser) AND Hereditary insensitivity to pain with anhidrosis

Germline classification:
Conflicting classifications of pathogenicity (4 submissions)
Last evaluated:
Jun 23, 2022
Review status:
criteria provided, conflicting classifications
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:
RCV000986439.17

Allele description [Variation Report for NM_001007792.1(NTRK1):c.163C>A (p.Arg55Ser)]

NM_001007792.1(NTRK1):c.163C>A (p.Arg55Ser)

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.163C>A (p.Arg55Ser)
HGVS:
  • NC_000001.11:g.156864394C>A
  • NG_007493.1:g.53645C>A
  • NM_001007792.1:c.163C>A
  • NM_001012331.2:c.253C>A
  • NM_002529.4:c.253C>AMANE SELECT
  • NP_001007793.1:p.Arg55Ser
  • NP_001012331.1:p.Arg85Ser
  • NP_001012331.1:p.Arg85Ser
  • NP_002520.2:p.Arg85Ser
  • LRG_261t1:c.163C>A
  • LRG_261t2:c.253C>A
  • LRG_261:g.53645C>A
  • LRG_261p1:p.Arg55Ser
  • LRG_261p2:p.Arg85Ser
  • NC_000001.10:g.156834186C>A
  • NM_001012331.1:c.253C>A
Protein change:
R55S
Links:
OMIM: 191315.0006; dbSNP: rs543320028
NCBI 1000 Genomes Browser:
rs543320028
Molecular consequence:
  • NM_001012331.2:c.253C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary insensitivity to pain with anhidrosis (CIPA)
Synonyms:
INSENSITIVITY TO PAIN, CONGENITAL, WITH ANHIDROSIS; FAMILIAL DYSAUTONOMIA, TYPE II; 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
SCV001135440Mendelics
criteria provided, single submitter

(Mendelics Assertion Criteria 2017)
Likely pathogenic
(May 28, 2019)
unknownclinical testing

Citation Link,

SCV001520942Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Mar 5, 2020)
unknownclinical testing

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

SCV002086502Natera, Inc.
no assertion criteria provided
Uncertain significance
(Feb 13, 2020)
germlineclinical testing

SCV002252424Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jun 23, 2022)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor.

Mardy S, Miura Y, Endo F, Matsuda I, Sztriha L, Frossard P, Moosa A, Ismail EA, Macaya A, Andria G, Toscano E, Gibson W, Graham GE, Indo Y.

Am J Hum Genet. 1999 Jun;64(6):1570-9.

PubMed [citation]
PMID:
10330344
PMCID:
PMC1377900
See all PubMed Citations (5)

Details of each submission

From Mendelics, SCV001135440.1

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

From Baylor Genetics, SCV001520942.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Natera, Inc., SCV002086502.1

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002252424.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 85 of the NTRK1 protein (p.Arg85Ser). This variant is present in population databases (rs543320028, gnomAD 0.003%). This missense change has been observed in individual(s) with congenital insensitivity to pain with anhidrosis (PMID: 10330344, 32707409). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 584593). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NTRK1 protein function. Experimental studies have shown that this missense change does not substantially affect NTRK1 function (PMID: 11719521). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

Last Updated: Jan 19, 2025