ClinVar Miner

Submissions for variant NM_015560.2(OPA1):c.2708_2711delTTAG (rs80356530)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000081763 SCV000228466 pathogenic not provided 2017-01-12 criteria provided, single submitter clinical testing
GeneDx RCV000081763 SCV000252013 pathogenic not provided 2017-11-02 criteria provided, single submitter clinical testing The c.2708_2711delTTAG variant has been reported multiple times in association with autosomal dominant optic atrophy (Delettre et al., 2000; Toomes et al., 2001). This variant has also been reported in a patient with optic atrophy plus spastic paraplegia, Duane retraction syndrome, migraine with atypical aura, patent foramen ovale, and muscle fibre abnormalities (Pretegiani et al., 2011). 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). The deletion causes a frameshift starting with codon Valine 903, changes this amino acid to a Glycine residue and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Val903GlyfsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret c.2708_2711delTTAG to be a pathogenic variant.
Athena Diagnostics Inc RCV000081763 SCV000614384 pathogenic not provided 2015-09-18 criteria provided, single submitter clinical testing
Center of Genomic medicine, Geneva,University Hospital of Geneva 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
CeGaT Praxis fuer Humangenetik Tuebingen RCV000081763 SCV001246487 pathogenic not provided 2020-02-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000081763 SCV001446520 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich 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 2020-10-08 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. This variant is present in population databases (rs745560444, ExAC 0.01%). This variant has been observed in individual(s) with dominant optic atrophy (PMID: 11017079, 26385429). It has also been observed to segregate with disease in related individuals. It is also known as c.2708delTTAG in the literature. ClinVar contains an entry for this variant (Variation ID: 5082). Loss-of-function variants in OPA1 are known to be pathogenic (PMID: 11440988, 20157015, 20952381, 25012220). For these reasons, this variant has been classified as Pathogenic.
Genomics England Pilot Project,Genomics England RCV001542739 SCV001760119 likely pathogenic Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy criteria provided, single submitter clinical testing
OMIM RCV000005387 SCV000025567 pathogenic Autosomal dominant optic atrophy classic form 2011-08-01 no assertion criteria provided literature only
GeneReviews RCV000005387 SCV000041284 pathogenic Autosomal dominant optic atrophy classic form 2015-11-12 no assertion criteria provided literature only
OMIM RCV000210745 SCV000266834 pathogenic Abortive cerebellar ataxia 2011-08-01 no assertion criteria provided literature only
Wellcome Centre for Mitochondrial Research,Newcastle University RCV000508703 SCV000575923 pathogenic Mitochondrial diseases 2017-04-07 no assertion criteria provided clinical testing
GenomeConnect, ClinGen RCV000005387 SCV000606947 not provided Autosomal dominant optic atrophy classic form no assertion provided phenotyping only 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.

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