ClinVar Miner

Submissions for variant NM_000516.7(GNAS):c.226G>C (p.Asp76His)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center RCV004785218 SCV005397847 uncertain significance Pseudohypoparathyroidism type 1C 2024-03-11 criteria provided, single submitter clinical testing This sequence variant is a single nucleotide substitution (G>C) at position 226 of the coding sequence of the GNAS gene that results in an aspartic acid to histidine amino acid change at residue 76 of the Gs alpha subunit protein. This variant is absent from ClinVar and has not been reported in the literature in individuals with GNAS-related disease, to our knowledge. This variant is present in 5/1461686 alleles (0.0003421%) in the gnomAD v4.0.0 population database. Multiple bioinformatic tools predict that this amino acid change would be damaging, and the Asp76 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: PM2, PP3

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