ClinVar Miner

Submissions for variant NM_000516.7(GNAS):c.502G>A (p.Glu168Lys)

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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 RCV003064613 SCV003443378 likely pathogenic not provided 2023-03-10 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GNAS protein function. ClinVar contains an entry for this variant (Variation ID: 2138361). This variant is also known as p.E169K. This missense change has been observed in individuals with Albright’s Hereditary Osteodystrophy and/or pseudohypoparathyroidism type 1a (PMID: 25802881, 31286103; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 168 of the GNAS protein (p.Glu168Lys).
GeneDx RCV003064613 SCV004168227 uncertain significance not provided 2023-04-04 criteria provided, single submitter clinical testing Variant has been reported in the literature in individuals with an atypical presentation of GNAS-related disorder (Munteanu et al., 2019) or with limited clinical details and molecular assessment (Thiele et al., 2015); 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; This variant is associated with the following publications: (PMID: 25802881, 31286103)

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