Total submissions: 30
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000081763 | SCV000228466 | pathogenic | not provided | 2017-01-12 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000081763 | SCV000252013 | pathogenic | not provided | 2020-02-24 | criteria provided, single submitter | clinical testing | An Opa1 mouse model carrying the c.2708_2711delTTAG variant displayed a multi-systemic poly-degenerative phenotype including signs of visual failure, deafness, encephalomyopathy, peripheral neuropathy, ataxia, cardiomyopathy, and premature age-related axonal and myelin degenerations (Sarzi et al., 2012); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 23665194, 25012220, 26031781, 21646330, 25699009, 26385429, 27260406, 25564500, 23250881, 27974645, 11017079, 28848318, 15505825, 20952381, 11440989, 32025183, 31500643, 31589614, 33300680) |
Athena Diagnostics | RCV000081763 | SCV000614384 | pathogenic | not provided | 2022-12-07 | criteria provided, single submitter | clinical testing | This variant is expected to result in the loss of a functional protein. This variant is one of the most common pathogenic variants associated with autosomal dominant optic atrophy (ADOA; PMID: 11440989, 22857269), and therefore the frequency of this variant in the general population is consistent with pathogenicity (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This variant has been reported to exhibit reduced penetrance (PMID: 11440989). Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 18222991) This variant occurs with an alternate explanation for disease significantly less often than expected, suggesting this variant may be associated with disease. |
Center of Genomic medicine, |
RCV000005387 | SCV000693465 | pathogenic | Autosomal dominant optic atrophy classic form | 2017-09-18 | criteria provided, single submitter | clinical testing | This frameshift variant (deletion of four nucleotides) in the OPA1 gene was identified in a male young patient and also his mother, both diagnosed with optic atrophy 1. |
Blueprint Genetics | RCV001073751 | SCV001239311 | pathogenic | Retinal dystrophy | 2017-10-12 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000081763 | SCV001246487 | pathogenic | not provided | 2021-07-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV000081763 | SCV001446520 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, |
RCV000005387 | SCV001519161 | pathogenic | Autosomal dominant optic atrophy classic form | 2021-01-04 | criteria provided, single submitter | research | |
Institute of Medical Molecular Genetics, |
RCV000005387 | SCV001548160 | likely pathogenic | Autosomal dominant optic atrophy classic form | 2021-01-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000081763 | SCV001591733 | pathogenic | not provided | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val903Glyfs*3) in the OPA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OPA1 are known to be pathogenic (PMID: 11440988, 20157015, 20952381, 25012220). This variant is present in population databases (rs745560444, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with dominant optic atrophy (PMID: 11017079, 26385429). It has also been observed to segregate with disease in related individuals. This variant is also known as c.2708delTTAG and c.2873_2876delTTAG (p.V958Gfs*3). ClinVar contains an entry for this variant (Variation ID: 5082). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Genomics England Pilot Project, |
RCV001542739 | SCV001760119 | likely pathogenic | Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy | criteria provided, single submitter | clinical testing | ||
3billion | RCV000005387 | SCV002318897 | pathogenic | Autosomal dominant optic atrophy classic form | 2022-03-22 | criteria provided, single submitter | clinical testing | Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 20417570, 14961560). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Institute of Human Genetics, |
RCV002287324 | SCV002577870 | pathogenic | Optic nerve dysplasia | 2021-10-04 | criteria provided, single submitter | clinical testing | ACMG categories: PVS1,PP1,PP4,PP5 |
MGZ Medical Genetics Center | RCV000005387 | SCV002579707 | pathogenic | Autosomal dominant optic atrophy classic form | 2021-11-26 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002490322 | SCV002777553 | pathogenic | Abortive cerebellar ataxia; Glaucoma, normal tension, susceptibility to; Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy; Autosomal dominant optic atrophy classic form; Mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type) | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Al Jalila Children's Genomics Center, |
RCV000081763 | SCV002818199 | pathogenic | not provided | 2022-12-17 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000081763 | SCV003824243 | pathogenic | not provided | 2022-01-12 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000005387 | SCV004032248 | pathogenic | Autosomal dominant optic atrophy classic form | 2023-08-23 | criteria provided, single submitter | clinical testing | Criteria applied: PVS1,PS4,PS3_MOD |
Institute of Human Genetics Munich, |
RCV000005387 | SCV004045808 | pathogenic | Autosomal dominant optic atrophy classic form | 2023-08-17 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004532291 | SCV004120905 | pathogenic | OPA1-related disorder | 2023-08-31 | criteria provided, single submitter | clinical testing | The OPA1 c.2873_2876delTTAG variant is predicted to result in a frameshift and premature protein termination (p.Val958Glyfs*3). This variant is also often denoted as c.2708_2711delTTAG (p.Val903Glyfs*3) in the alternate transcript NM_015560.2. This variant has been reported many times as causative for autosomal dominant optic atrophy (see for examples Delettre et al. 2000. PubMed ID: 11017079; Pretegiani et al. 2011. PubMed ID: 21646330; Gaier et al. 2017. PubMed ID: 28848318; Lin et al. 2021. PubMed ID: 34573359). This variant has also been reported in the compound heterozygous state in an individual with early-onset Behr syndrome and the unaffected mother was a carrier of this variant, suggesting there may be incomplete penetrance (Bonneau et al. 2014. PubMed ID: 25012220). This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-193384956-CAGTT-C). Frameshift variants in OPA1 are expected to be pathogenic, and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/5082). Given all the evidence, we interpret c.2873_2876del (p.Val958Glyfs*3) as pathogenic. |
Mayo Clinic Laboratories, |
RCV000081763 | SCV004226069 | pathogenic | not provided | 2022-10-21 | criteria provided, single submitter | clinical testing | PP1, PS4, PVS1 |
OMIM | RCV000005387 | SCV000025567 | pathogenic | Autosomal dominant optic atrophy classic form | 2011-08-01 | no assertion criteria provided | literature only | |
Gene |
RCV000005387 | SCV000041284 | not provided | Autosomal dominant optic atrophy classic form | no assertion provided | literature only | ||
OMIM | RCV000210745 | SCV000266834 | pathogenic | Abortive cerebellar ataxia | 2011-08-01 | no assertion criteria provided | literature only | |
Wellcome Centre for Mitochondrial Research, |
RCV000508703 | SCV000575923 | pathogenic | Mitochondrial disease | 2017-04-07 | no assertion criteria provided | clinical testing | |
Genome |
RCV000005387 | SCV000606947 | not provided | Autosomal dominant optic atrophy classic form | no assertion provided | phenotyping only | Variant was identified in multiple participants. Variant interpreted as Pathogenic and reported, most recently, on 11-07-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. | |
Clinical Genetics, |
RCV000081763 | SCV001921462 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000081763 | SCV001974149 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Al Jalila Children's Genomics Center, |
RCV000005387 | SCV001984459 | pathogenic | Autosomal dominant optic atrophy classic form | 2020-10-18 | flagged submission | clinical testing | |
Practice for Gait Abnormalities, |
RCV003319160 | SCV004023198 | likely pathogenic | Tip-toe gait | 2022-11-23 | no assertion criteria provided | clinical testing |