Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000988396 | SCV001138099 | likely pathogenic | Amyotrophic lateral sclerosis type 23 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002549708 | SCV003012444 | pathogenic | not provided | 2022-04-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp40 amino acid residue in ANXA11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28469040, 29845112, 33087501). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 802593). This missense change has been observed in individuals with ANXA11-related conditions (PMID: 34048612). It has also been observed to segregate with disease in related individuals. This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 40 of the ANXA11 protein (p.Asp40Tyr). |
| 3billion | RCV001836926 | SCV003841270 | pathogenic | Inclusion body myopathy and brain white matter abnormalities | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism.Same nucleotide change resulting in same amino acid change has been previously reported to be associated with ANXA11 related disorder (ClinVar ID: VCV000802593). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 34048612 / 3billion dataset). The variant has been reported to co-segregate with the disease in at least 7 similarly affected relatives/individuals in at least two unrelated families (PMID: 34048612). A different missense change at the same codon (p.Asp40Gly) has been reported to be associated with ANXA11 related disorder (ClinVar ID: VCV000488353 / PMID: 28469040). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| OMIM | RCV001836926 | SCV002097624 | pathogenic | Inclusion body myopathy and brain white matter abnormalities | 2022-02-15 | no assertion criteria provided | literature only |