NM_002529.4(NTRK1):c.2239G>A (p.Glu747Lys) AND Hereditary insensitivity to pain with anhidrosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 18, 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:: RCV001295666.7

Allele description [Variation Report for NM_002529.4(NTRK1):c.2239G>A (p.Glu747Lys)]

NM_002529.4(NTRK1):c.2239G>A (p.Glu747Lys)

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.2239G>A (p.Glu747Lys)

HGVS:

NC_000001.11:g.156881490G>A
NG_007493.1:g.70741G>A
NM_001007792.1:c.2131G>A
NM_001012331.2:c.2221G>A
NM_002529.4:c.2239G>AMANE SELECT
NP_001007793.1:p.Glu711Lys
NP_001012331.1:p.Glu741Lys
NP_002520.2:p.Glu747Lys
LRG_261t1:c.2131G>A
LRG_261:g.70741G>A
LRG_261p1:p.Glu711Lys
NC_000001.10:g.156851282G>A

Protein change:

E711K

Links:

dbSNP: rs1648255941

NCBI 1000 Genomes Browser:

rs1648255941

Molecular consequence:

NM_001007792.1:c.2131G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001012331.2:c.2221G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002529.4:c.2239G>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001484601	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 18, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001484601

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 18, 2020)

germline

clinical testing

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

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001484601.4

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NTRK1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 741 of the NTRK1 protein (p.Glu741Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. 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.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine