Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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 |