Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000756731 | SCV000884625 | likely pathogenic | not provided | 2017-06-19 | criteria provided, single submitter | clinical testing | The c.842_843del variant (rs748900391) has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. It is listed in the Exome Aggregation Consortium (ExAC) browser with an overall frequency of 0.0008 percent (identified in 1 out of 121,266 chromosomes). The c.842_843del variant introduces a frameshift into the terminal exon (exon 6) and is predicted to result in a truncated protein product. While this variant is not predicted to induce nonsense mediated mRNA decay, it nonetheless removes the dimerization domain, and other truncating variants that also remove this domain have been identified in patients with clinical symptoms of sulfite oxidase deficiency (Johnson 2002). Therefore, based on the available information, the c.842_843del variant is likely to be pathogenic. |
Ambry Genetics | RCV001267499 | SCV001445680 | pathogenic | Inborn genetic diseases | 2018-03-08 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155304 | SCV003844612 | likely pathogenic | Sulfocysteinuria | 2023-02-13 | criteria provided, single submitter | clinical testing | Variant summary: SUOX c.842_843delTG (p.Leu281ArgfsX19) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been associated with Sulfite Oxidase deficiency in HGMD. The variant allele was found at a frequency of 4e-06 in 251372 control chromosomes. To our knowledge, no occurrence of c.842_843delTG in individuals affected with Sulfite Oxidase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic (n=1) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |