ClinVar Miner

Submissions for variant NM_001077488.4(GNAS):c.1A>G (p.Met1Val) (rs137854530)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763448 SCV000894224 pathogenic Cushing's 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
GeneDx RCV000522303 SCV000617421 likely pathogenic not provided 2017-10-12 criteria provided, single submitter clinical testing The c.1 A>G variant in the GNAS gene has been reported previously in a proband with pseudohypoparathyroidism type Ia and his mother with pseudopseudohypoparathyroidism (Patten et al., 1990). As this variant changes the translation initiator Methionine codon, the resultant protein is described as p.Met1?, using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. Other variants in the initiator Methionine codon (c.2 T>G, c.3 G>A) have been reported in individuals with features of Albright hereditary osteodystrophy (Long et al., 2007; Puzhko et al., 2011; Fernandez-Rebollo et al., 2013). The c.1 A>G variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1 A>G as a likely pathogenic variant. The presence of this variant is consistent with the reported learning disability and short stature in this individual.
OMIM RCV000017278 SCV000037550 pathogenic Pseudohypoparathyroidism 1990-05-17 no assertion criteria provided literature only

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