ClinVar Miner

Submissions for variant NM_000516.7(GNAS):c.389A>G (p.Tyr130Cys)

dbSNP: rs2146184314
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002265100 SCV002546632 pathogenic not provided 2023-08-11 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33730787)
Neuberg Centre For Genomic Medicine, NCGM RCV003447623 SCV004175835 uncertain significance Pseudohypoparathyroidism type I A 2023-02-14 criteria provided, single submitter clinical testing The missense c.389A>G(p.Tyr130Cys) variant in GNAS gene has been reported previously in heterozygous state in an individual (as a De-novo variant) affected with Pseudohypoparathyroidism type 1A (Kotanidou EP, et. al., 2021). The p.Tyr130Cys variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The amino acid change p.Tyr130Cys in GNAS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Tyr at position 130 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. Additional functional studies are required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).

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