ClinVar Miner

Submissions for variant NM_000233.4(LHCGR):c.562G>T (p.Glu188Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002664238 SCV003524645 pathogenic not provided 2024-10-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu188*) in the LHCGR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LHCGR are known to be pathogenic (PMID: 25383892, 27016457). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with 46, XY disorder of sex development (PMID: 25383892). ClinVar contains an entry for this variant (Variation ID: 2203075). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005059182 SCV005725926 pathogenic Leydig cell agenesis 2024-11-01 criteria provided, single submitter clinical testing Variant summary: LHCGR c.562G>T (p.Glu188X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251130 control chromosomes. c.562G>T has been reported in the literature as a homozygous genotype in at-least one individual affected with features of Leydig Cell Hypoplasia, specifically a 46,XY disorder of sex development (example, Baxter_2014) from a reportedly consanguineous family. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 2203075). The following publication have been ascertained in the context of this evaluation (PMID: 25383892). Based on the evidence outlined above, the variant was classified as pathogenic.

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