ClinVar Miner

Submissions for variant NM_000516.7(GNAS):c.1A>G (p.Met1Val)

dbSNP: rs137854530
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522303 SCV000617421 likely pathogenic not provided 2021-07-15 criteria provided, single submitter clinical testing Initiation codon variants (Met1?) in GNAS likely lead to the use of an alternate initiation codon and the loss of the first 59 residues (Patten JL et al., 1990; Puzhko S et al., 2011); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 2109828, 27535533, 31546270)
Fulgent Genetics, Fulgent Genetics RCV000763448 SCV000894224 pathogenic Cushing syndrome; McCune-Albright syndrome; Pseudohypoparathyroidism; Pseudohypoparathyroidism type 1C; Pseudohypoparathyroidism type 1B; Pseudopseudohypoparathyroidism; Progressive osseous heteroplasia; Pituitary adenoma 3, multiple types 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000522303 SCV003443842 pathogenic not provided 2023-08-10 criteria provided, single submitter clinical testing Experimental studies have shown that disruption of the initiator codon affects GNAS function (PMID: 21713996). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This sequence change affects the initiator methionine of the GNAS mRNA. The next in-frame methionine is located at codon 60. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with Albright’s hereditary osteodystrophy (PMID: 2109828, 21713996). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 15927).
OMIM RCV000017278 SCV000037550 pathogenic Pseudohypoparathyroidism 1990-05-17 no assertion criteria provided literature only

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