ClinVar Miner

Submissions for variant NM_003172.4(SURF1):c.833+1G>A (rs782609482)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781906 SCV000920300 pathogenic not specified 2018-08-06 criteria provided, single submitter clinical testing Variant summary: SURF1 c.833+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: five predict the variant abolishes a 5 prime splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 241660 control chromosomes (gnomAD). The variant, c.833+1G>A has been reported in the literature in 2 homozygous individuals affected with Leigh Syndrome (Lee 2012, Wedatilake 2013). These data indicate that the variant is likely to be associated with disease. One of these publications also reported experimental evidence, demonstrating 40% of normal cytochrome c oxidase (COX) activity in fibroblasts, and the absence of COX in skeletal muscles (Wedatilake 2013). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000735985 SCV000863564 pathogenic Leigh syndrome 2018-12-19 no assertion criteria provided clinical testing The observed variant NG_008477.1:g.9447G>A has not been reported in the 1000 genomes and ExAC databases. The in silico prediction of this variant is damaging by MutationTaster2.

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