Submissions for variant NM_000823.4(GHRHR):c.847T>C (p.Trp283Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004702944	SCV005203844	likely pathogenic	Isolated growth hormone deficiency, type 4	2024-07-30	criteria provided, single submitter	clinical testing	Variant summary: GHRHR c.847T>C (p.Trp283Arg) results in a non-conservative amino acid change located in the GPCR, family 2-like, 7TM domain (IPR017981) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251484 control chromosomes. c.847T>C has been reported in the literature in at least one homozygous individual affected with Isolated growth hormone deficiency with no detected GH1 variant (e.g. Cohen_2019). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in near complete loss of cAMP signaling activity in vitro (e.g. Cohen_2019). The following publication has been ascertained in the context of this evaluation (PMID: 31231873). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.