ClinVar Miner

Submissions for variant NM_001354663.2(OPA1):c.-260_-243del (rs863224140)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487644 SCV000252008 uncertain significance not provided 2018-07-16 criteria provided, single submitter clinical testing The c.113_130del18 variant in the OPA1 gene has been reported previously in association with optic atrophy (Thiselton et al., 2002; Almind et al., 2012), and has also been reported in a patient with a more severe phenotype that included ptosis, limited eye movements, hearing loss and multiple muscle mtDNA deletions without optic atrophy (Milone et al., 2009). The c.113_130del18 deletion causes the loss of six amino acids beginning with Arginine 38 and ending with Serine 43, denoted p.Arg38_Ser43del. Furthermore, the deleted interval includes the first predicted cleavage site of the mitochondrial leader sequence and may therefore affect the correct targeting of the OPA1 protein to the mitochondria (Thiselton et al., 2002). The c.113_130del18 variant is observed in 237/66,724 (0.35%) alleles from individuals of European (non-Finnish) background including multiple unrelated homozygous individuals in the ExAC dataset (Lek et al., 2016). We interpret c.113_130del18 as a variant of uncertain significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000487644 SCV000331095 uncertain significance not provided 2016-02-12 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415438 SCV000492829 uncertain significance Elevated serum creatine phosphokinase; Muscle weakness; Ptosis; Hypomimic face; Hepatic steatosis; EMG abnormality; EMG: myopathic abnormalities; EMG: myotonic runs; Progressive proximal muscle weakness 2015-04-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487644 SCV000575383 uncertain significance not provided 2019-09-01 criteria provided, single submitter clinical testing
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000489905 SCV000575933 uncertain significance Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 2017-04-25 criteria provided, single submitter clinical testing This variant has been identified at an allele frequency of 0.22% in both ExAC overall and in European Americans in ESP; three homozygous individuals have been identified in these databases combined. However, this condition exhibits marked variable expressivity and incomplete penetrance, and compound heterozygous individuals have been reported with milder pathogenic variants. A previously reported patient (Milone, 2009) had a similar presentation to the patient observed in our clinic, but family segregation studies were not done in that case. The patient tested in our clinic presented with fatigue, ataxia, muscle weakness, peripheral neuropathy, ptosis, and external ophthalmoplegia. She did not have optic atrophy at age 51. Her mother had a similar clinical presentation and was deceased. The patient is also an FMR1 premutation carrier. This OPA1 variant was inherited from her father, who at age 74, had no clinical symptoms of neurological or mitochondrial dysfunction, although he had a history of migraines.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000487644 SCV000610798 uncertain significance not provided 2017-04-04 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000197686 SCV000614370 benign not specified 2017-07-17 criteria provided, single submitter clinical testing
Invitae RCV000487644 SCV001117421 likely benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197504 SCV001368272 uncertain significance Abortive cerebellar ataxia 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM4.

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