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NM_001007792.1(NTRK1):c.163C>A (p.Arg55Ser) AND Inborn genetic diseases

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 31, 2020
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:
RCV002424729.9

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:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002742454Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Dec 31, 2020) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

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

Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor.

Mardy S, Miura Y, Endo F, Matsuda I, Indo Y.

Hum Mol Genet. 2001 Feb 1;10(3):179-88.

PubMed [citation]
PMID:
11159935
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002742454.2

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

Description

The p.R85S variant (also known as c.253C>A), located in coding exon 2 of the NTRK1 gene, results from a C to A substitution at nucleotide position 253. The arginine at codon 85 is replaced by serine, an amino acid with dissimilar properties. This variant was detected in the homozygous state in an individual with congenital insensitivity to pain with anhidrosis (CIPA) who also had another homozygous variant in NTRK1 (c.429-1G>C) (Mardy S et al. Am J Hum Genet, 1999 Jun;64:1570-9). In addition, the p.R85S variant was found to segregate with CIPA in two affected siblings with CIPA, who were both compound heterozygotes for NTRK1 p.R85S (c.253C>A) and p.R692C (c.2074C>T) (Hartono F et al. Int J Surg Case Rep, 2020 Jul;73:213-217). Protein functional studies suggest that this alteration does not impair normal processing or autophosphorylation of NTRK1 (Mardy S et al. Hum Mol Genet, 2001 Feb;10:179-88; Miranda C et al. J Biol Chem, 2002 Feb;277:6455-62). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Jan 19, 2025