Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001853834 | SCV002119960 | pathogenic | not provided | 2023-01-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ANXA11 function (PMID: 28469040, 33087501). 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: 488353). This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 28469040, 29845112, 33087501). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 40 of the ANXA11 protein (p.Asp40Gly). |
OMIM | RCV000578138 | SCV000679995 | pathogenic | Amyotrophic lateral sclerosis type 23 | 2018-01-29 | no assertion criteria provided | literature only | |
Prevention |
RCV003403366 | SCV004103073 | pathogenic | ANXA11-related disorder | 2024-01-16 | no assertion criteria provided | clinical testing | The ANXA11 c.119A>G variant is predicted to result in the amino acid substitution p.Asp40Gly. This variant has been reported in individuals with amyotrophic lateral sclerosis (ALS) or ALS-frontotemporal dementia (ALS-FTD) (Smith et al. 2017. PubMed ID: 28469040; Zhang et al. 2018. PubMed ID: 29845112; Nahm et al. 2020. PubMed ID: 33087501; Wang et al. 2022. PubMed ID: 36226077). It was reported to segregate with disease in at least two families (Smith et al. 2017. PubMed ID: 28469040). Experimental studies are consistent with the p.Asp40Gly substitution impacting protein function (Smith et al. 2017. PubMed ID: 28469040; Nahm et al. 2020. PubMed ID: 33087501). This variant is reported in 0.0023% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. |