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NM_000233.4(LHCGR):c.1624A>C (p.Ile542Leu) AND LHCGR-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 13, 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:
RCV003407338.4

Allele description [Variation Report for NM_000233.4(LHCGR):c.1624A>C (p.Ile542Leu)]

NM_000233.4(LHCGR):c.1624A>C (p.Ile542Leu)

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.1624A>C (p.Ile542Leu)
HGVS:
  • NC_000002.12:g.48688173T>G
  • NG_008193.2:g.72569A>C
  • NG_033050.2:g.163249T>G
  • NM_000233.4:c.1624A>CMANE SELECT
  • NM_001198593.2:c.3441+16493T>G
  • NP_000224.2:p.Ile542Leu
  • NC_000002.11:g.48915312T>G
  • NM_000233.3:c.1624A>C
  • P22888:p.Ile542Leu
Protein change:
I542L; ILE542LEU
Links:
UniProtKB: P22888#VAR_010157; OMIM: 152790.0018; dbSNP: rs121912531
NCBI 1000 Genomes Browser:
rs121912531
Molecular consequence:
  • NM_001198593.2:c.3441+16493T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000233.4:c.1624A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
LHCGR-related disorder
Synonyms:
LHCGR-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004114141PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Oct 13, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004114141.1

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

Description

The LHCGR c.1624A>C variant is predicted to result in the amino acid substitution p.Ile542Leu. This variant has been reported in multiple individuals from unrelated families with male precocious puberty (Laue et al. 1995. PubMed ID: 7892197; Kooij CD et al 2022. PubMed ID: 36071555). In vitro functional studies showed that this variant has increased constitutive activity compared to wild-type LHCGR and appeared ligand-unresponsive (Laue et al. 1995. PubMed ID: 7892197). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.

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

Last Updated: Sep 29, 2024