NM_023110.3(FGFR1):c.523A>G (p.Lys175Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 25, 2023
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:: RCV003803855.4

Allele description [Variation Report for NM_023110.3(FGFR1):c.523A>G (p.Lys175Glu)]

NM_023110.3(FGFR1):c.523A>G (p.Lys175Glu)

Gene:

FGFR1:fibroblast growth factor receptor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p11.23

Genomic location:

Preferred name:

NM_023110.3(FGFR1):c.523A>G (p.Lys175Glu)

HGVS:

NC_000008.11:g.38428019T>C
NG_007729.1:g.45816A>G
NG_113991.1:g.449T>C
NM_000604.2:c.523A>G
NM_001174063.2:c.523A>G
NM_001174064.2:c.499A>G
NM_001174065.2:c.517A>G
NM_001174066.2:c.256A>G
NM_001174067.2:c.616A>G
NM_001354367.2:c.517A>G
NM_001354368.2:c.250A>G
NM_001354369.2:c.517A>G
NM_001354370.2:c.250A>G
NM_001410922.1:c.517A>G
NM_015850.4:c.517A>G
NM_023105.3:c.256A>G
NM_023106.3:c.250A>G
NM_023110.3:c.523A>GMANE SELECT
NP_000595.1:p.Lys175Glu
NP_001167534.1:p.Lys175Glu
NP_001167535.1:p.Lys167Glu
NP_001167536.1:p.Lys173Glu
NP_001167537.1:p.Lys86Glu
NP_001167538.1:p.Lys206Glu
NP_001341296.1:p.Lys173Glu
NP_001341297.1:p.Lys84Glu
NP_001341298.1:p.Lys173Glu
NP_001341299.1:p.Lys84Glu
NP_001397851.1:p.Lys173Glu
NP_056934.2:p.Lys173Glu
NP_075593.1:p.Lys86Glu
NP_075594.1:p.Lys84Glu
NP_075598.2:p.Lys175Glu
NP_075598.2:p.Lys175Glu
LRG_993t1:c.523A>G
LRG_993:g.45816A>G
LRG_993p1:p.Lys175Glu
NC_000008.10:g.38285537T>C
NM_023110.2:c.523A>G

Protein change:

K167E

Links:

dbSNP: rs2150915367

Molecular consequence:

NM_000604.2:c.523A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001174063.2:c.523A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001174064.2:c.499A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001174065.2:c.517A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001174066.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001174067.2:c.616A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354367.2:c.517A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354368.2:c.250A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354369.2:c.517A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354370.2:c.250A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001410922.1:c.517A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015850.4:c.517A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_023105.3:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_023106.3:c.250A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_023110.3:c.523A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypogonadotropic hypogonadism 2 with or without anosmia (HH2)
Synonyms:: HYPOGONADOTROPIC HYPOGONADISM 2 WITHOUT ANOSMIA; HYPOGONADOTROPIC HYPOGONADISM 2 WITH OR WITHOUT ANOSMIA, SUSCEPTIBILITY TO; HYPOGONADOTROPIC HYPOGONADISM 2 WITHOUT ANOSMIA, SUSCEPTIBILITY TO
Identifiers:: MONDO: MONDO:0007844; MedGen: C1563720; Orphanet: 478; OMIM: 147950

Name:: Pfeiffer syndrome (ACS5)
Synonyms:: ACS V
Identifiers:: MONDO: MONDO:0007043; MedGen: C0220658; Orphanet: 710; OMIM: 101600

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
SCV004591290	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 25, 2023)	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

SCV004591290

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 25, 2023)

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, SCV004591290.3

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

Description

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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FGFR1 protein function. This variant has not been reported in the literature in individuals affected with FGFR1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 175 of the FGFR1 protein (p.Lys175Glu).

#	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: Feb 23, 2026

ClinVar

Relating variation to medicine