ClinVar Miner

Submissions for variant NM_078470.6(COX15):c.*1126T>C

gnomAD frequency: 0.84288  dbSNP: rs2231687
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000116814 SCV000168013 benign not specified 2011-07-01 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services,Illumina RCV000259999 SCV000359736 benign Leigh syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000116814 SCV000917264 benign not specified 2018-09-10 criteria provided, single submitter clinical testing Variant summary: COX15 c.1120T>C (p.Phe374Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.86 in 273702 control chromosomes (gnomAD), suggesting that it is the major allele and therefore benign. The observed variant frequency is approximately 690-fold higher than the estimated maximal expected allele frequency for a pathogenic variant in COX15 causing Leigh Syndrome phenotype (0.0013), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1120T>C in individuals affected with Leigh Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submission from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000676871 SCV001727390 benign not provided 2021-12-15 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000116814 SCV000150888 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Mayo Clinic Laboratories,Mayo Clinic RCV000676871 SCV000802684 benign not provided 2016-02-15 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000116814 SCV001742491 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000116814 SCV001956636 benign not specified no assertion criteria provided clinical testing

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