Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001786848 | SCV002028811 | uncertain significance | not provided | 2021-05-27 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27535533) |
| Victorian Clinical Genetics Services, |
RCV004785313 | SCV005400008 | uncertain significance | ALDH18A1-related de Barsy syndrome | 2021-05-06 | 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: 0103 - Dominant negative and loss of function and are known mechanisms of disease in this gene. Loss of function is commonly associated with Spastic paraplegia 9B while dominant negative is a mechanism associated with Spastic paraplegia 9A (PMID: 31402623). (I) 0108 - This gene is associated with both recessive (Cutis laxa type IIIA MIM#219150, Spastic paraplegia 9B MIM#616586) and dominant disease (Cutis laxa 3 MIM#616603, Spastic paraplegia 9A MIM#601162), although no clear genotype-phenotype correlations have been observed (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to arginine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (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 Aldehyde dehydrogenase family (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) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |