ClinVar Miner

Submissions for variant NM_000516.7(GNAS):c.317T>C (p.Ile106Thr)

dbSNP: rs2517082005
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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 RCV003064612 SCV003443845 pathogenic not provided 2024-01-06 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 106 of the GNAS protein (p.Ile106Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pseudohypoparathyroidism and/or pseudopseudohypoparathyroidism (PMID: 21340160, 23884777). In at least one individual the variant was observed to be de novo. This variant is also known as c.320T>C (p.Ile107Thr). ClinVar contains an entry for this variant (Variation ID: 2138360). 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 with a negative predictive value of 80%. This variant disrupts the p.Ile106 amino acid residue in GNAS. Other variant(s) that disrupt this residue have been observed in individuals with GNAS-related conditions (PMID: 15817905, 21340160, 23884777; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Heidelberg University RCV005227807 SCV005871409 likely pathogenic GNAS-associated disease 2024-08-23 criteria provided, single submitter clinical testing

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