NM_002529.4(NTRK1):c.482G>A (p.Arg161His) AND Hereditary insensitivity to pain with anhidrosis

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 30, 2024
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:: RCV000547738.17

Allele description [Variation Report for NM_002529.4(NTRK1):c.482G>A (p.Arg161His)]

NM_002529.4(NTRK1):c.482G>A (p.Arg161His)

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.482G>A (p.Arg161His)

HGVS:

NC_000001.11:g.156868157G>A
NG_007493.1:g.57408G>A
NM_001007792.1:c.392G>A
NM_001012331.2:c.482G>A
NM_002529.4:c.482G>AMANE SELECT
NP_001007793.1:p.Arg131His
NP_001012331.1:p.Arg161His
NP_001012331.1:p.Arg161His
NP_002520.2:p.Arg161His
NP_002520.2:p.Arg161His
LRG_261t1:c.392G>A
LRG_261t2:c.482G>A
LRG_261t3:c.482G>A
LRG_261:g.57408G>A
LRG_261p1:p.Arg131His
LRG_261p2:p.Arg161His
LRG_261p3:p.Arg161His
NC_000001.10:g.156837949G>A
NM_001012331.1:c.482G>A
NM_002529.3:c.482G>A
p.Arg161His

Protein change:

R131H

Links:

dbSNP: rs150271893

NCBI 1000 Genomes Browser:

rs150271893

Molecular consequence:

NM_001007792.1:c.392G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001012331.2:c.482G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002529.4:c.482G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000626972	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 30, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001252344	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000626972

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 30, 2024)

germline

clinical testing

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

SCV001252344

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

c.1810C>T polymorphism of NTRK1 gene is associated with reduced survival in neuroblastoma patients.

Lipska BS, Drozynska E, Scaruffi P, Tonini GP, Izycka-Swieszewska E, Zietkiewicz S, Balcerska A, Perek D, Chybicka A, Biernat W, Limon J.

BMC Cancer. 2009 Dec 13;9:436. doi: 10.1186/1471-2407-9-436.

PubMed [citation]

PMID:: 20003389
PMCID:: PMC2800120

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000626972.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001252344.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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