Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004788459 | SCV005397991 | uncertain significance | Pseudohypoparathyroidism type I A | 2024-09-23 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0103 - Both loss- and gain-of-function are known mechanisms of disease for this gene. Loss-of-function has been associated with the hypoparathyroidism phenotypes (PMID: 10980525), while gain-of-function has been reported for somatic variants in cancers (PMID: 11588148). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0113 - This gene is known to be imprinted and the imprinting can be transcript dependent (OMIM, PMID: 23884777). (I) 0115 - Variants in this gene are known to have variable expressivity (GeneReviews). 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to valine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated G-protein alpha subunit (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |