NM_000233.4(LHCGR):c.1471T>C (p.Trp491Arg) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 24, 2017
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:: RCV000484363.1

Allele description [Variation Report for NM_000233.4(LHCGR):c.1471T>C (p.Trp491Arg)]

NM_000233.4(LHCGR):c.1471T>C (p.Trp491Arg)

Genes:

STON1-GTF2A1L:STON1-GTF2A1L readthrough [Gene - HGNC]
LHCGR:luteinizing hormone/choriogonadotropin receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000233.4(LHCGR):c.1471T>C (p.Trp491Arg)

HGVS:

NC_000002.12:g.48688326A>G
NG_008193.2:g.72416T>C
NG_033050.2:g.163402A>G
NM_000233.4:c.1471T>CMANE SELECT
NM_001198593.2:c.3441+16646A>G
NP_000224.2:p.Trp491Arg
NC_000002.11:g.48915465A>G
NM_000233.3:c.1471T>C

Protein change:

W491R

Links:

dbSNP: rs1064796476

NCBI 1000 Genomes Browser:

rs1064796476

Molecular consequence:

NM_001198593.2:c.3441+16646A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000233.4:c.1471T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000573240	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Feb 24, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000573240

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Feb 24, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000573240.4

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

Description

The W491R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The W491R variant is not observed in large population cohorts (Lek et al., 2016; Exome Variant Server). The W491R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the transmembrane helical region 4 that is conserved across species and in silico analysis predicts this variant is probably damaging the protein structure/function. Furthermore, W491 is proposed to be a critical residue in maintaining structural stability of the protein (Yariz et al. 2011). In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Sep 1, 2024

ClinVar

Relating variation to medicine