ClinVar Miner

Submissions for variant NM_000516.7(GNAS):c.1006C>T (p.Arg336Trp)

dbSNP: rs2146299968
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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 RCV002015767 SCV002292244 pathogenic not provided 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 336 of the GNAS protein (p.Arg336Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with pseudohypoparathyroidism and/or pseudopseudohypoparathyroidism (PMID: 11600516, 23281139, 29059381, 31886927). This variant is also known as c.1009C>T (p.Arg337Trp) in NM_001077488.2. ClinVar contains an entry for this variant (Variation ID: 1500589). 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 expected to disrupt GNAS protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV003138029 SCV003806869 likely pathogenic Pseudohypoparathyroidism type 1C 2022-09-17 criteria provided, single submitter clinical testing ACMG classification criteria: PS4 moderated, PM2 moderated, PP1 supporting, PP3 supporting

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