Submissions for variant NM_000516.7(GNAS):c.446A>G (p.His149Arg)

dbSNP: rs2146208770

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV002253068	SCV002523189	likely pathogenic	Pseudohypoparathyroidism type I A	2022-03-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004533998	SCV004107507	likely pathogenic	GNAS-related disorder	2023-08-01	criteria provided, single submitter	clinical testing	The GNAS c.446A>G variant is predicted to result in the amino acid substitution p.His149Arg. To our knowledge, this variant has not been reported in the literature or a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At PreventionGenetics, we have observed this variant to occur de novo in a patient with features of a GNAS-related disorder (internal data). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx	RCV004763344	SCV005373035	uncertain significance	not provided	2023-07-20	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge