ClinVar Miner

Submissions for variant NM_005138.3(SCO2):c.281T>C (p.Leu94Pro)

gnomAD frequency: 0.00003  dbSNP: rs138294250
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001588330 SCV001822656 likely pathogenic not provided 2023-11-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30340907, 34362006, 34732400)
Invitae RCV001588330 SCV003468749 uncertain significance not provided 2022-05-07 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 94 of the SCO2 protein (p.Leu94Pro). This variant is present in population databases (rs138294250, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SCO2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1219241). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV003147639 SCV003836158 likely pathogenic Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 2024-03-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003235591 SCV003933795 uncertain significance not specified 2023-05-05 criteria provided, single submitter clinical testing Variant summary: SCO2 c.281T>C (p.Leu94Pro) results in a non-conservative amino acid change located in the Thioredoxin domain (IPR013766) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 248648 control chromosomes. c.281T>C has been reported in the literature in individuals affected with Mitochondrial disorder (Schon_2021, Rubegni_2018). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34732400, 34362006, 30340907). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified as VUS (n=2) and Likely Pathogenic (n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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