Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004700243 | SCV005202828 | pathogenic | Idiopathic growth hormone deficiency | 2024-07-31 | criteria provided, single submitter | clinical testing | Variant summary: GH1 c.291+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. Multiple publication reports experimental evidence that this variant affects mRNA splicing, resulting in exon 3 skipping, confirmed in vivo and in vitro evidenced by shortened mRNA transcript length and cDNA sequencing products with absent exon 3 (e.g. Missarelli_HumGen_1997, Moseley_2002). The variant was absent in 251464 control chromosomes. c.291+5G>A has been reported in the literature in multiple heterozygous individuals affected with Autosomal Dominant Idiopathic Growth Hormone Deficiency, additionally showing segregation with disease in multiple families (e.g. Missarelli_HumGen_1997, Moseley_2002). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 9385381, 11836331). ClinVar contains an entry for this variant (Variation ID: 15975). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000017345 | SCV000037617 | pathogenic | Autosomal dominant isolated somatotropin deficiency | 1999-09-01 | no assertion criteria provided | literature only |