Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481980 | SCV000566962 | pathogenic | not provided | 2021-02-10 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect with significantly altered distribution of the ALDH18A1 protein within the mitochondrial network and reduced enzyme activity (Fischer-Zirnsak et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26320891) |
| Institute of Human Genetics, |
RCV000201215 | SCV001429364 | pathogenic | Cutis laxa, autosomal dominant 3 | 2019-09-05 | criteria provided, single submitter | clinical testing | This variant was identified as de novo (maternity and paternity confirmed). |
| 3billion | RCV000201215 | SCV002058701 | pathogenic | Cutis laxa, autosomal dominant 3 | 2022-01-03 | criteria provided, single submitter | clinical testing | The variantwas confirmed as de novo by parental testing. The same variant was also reported as de novo in one or more affected individuals with a consistent phenotype from multiple, unrelated families (PMID: 26320891) (PS2_VS). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000217259, PMID:26320891, PS1_S). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000217261, PMID:26320891,26320891, PM5_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.821, 3CNET: 0.985, PP3_P). A missense variant is a common mechanism associated with Cutis laxa (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Molecular Genetics Lab, |
RCV003883142 | SCV004697646 | pathogenic | ALDH18A1-related de Barsy syndrome; Hereditary spastic paraplegia 9A; Autosomal recessive complex spastic paraplegia type 9B; Cutis laxa, autosomal dominant 3 | criteria provided, single submitter | clinical testing | ||
| OMIM | RCV000201215 | SCV000255928 | pathogenic | Cutis laxa, autosomal dominant 3 | 2015-09-03 | no assertion criteria provided | literature only |