Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004788210 | SCV005398670 | uncertain significance | Amelogenesis imperfecta - hypoplastic autosomal dominant - local | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with amelogenesis imperfecta, type IC (MIM#204650), and amelogenesis imperfecta, type IB (MIM#104500). (I) 0108 - This gene is associated with both recessive and dominant disease. Autosomal recessive inheritance is associated with a more severe phenotype (PMID: 33864320). (I) 0112 - The condition associated with this gene has incomplete penetrance. Unaffected carriers of pathogenic variants have been described (PMID: 33864320). (I) 0115 - Variants in this gene are known to have variable expressivity. Intrafamilial variability of disease severity has been described (PMID: 12828988). (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to isoleucine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (3 heterozygotes, 0 homozygotes). (I) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (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) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |