ClinVar Miner

Submissions for variant NM_001308211.1(EARS2):c.322C>T (p.Arg108Trp) (rs376103091)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622765 SCV000742947 uncertain significance Inborn genetic diseases 2017-09-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000255688 SCV000511548 likely pathogenic not provided 2016-09-13 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626746 SCV000747449 pathogenic Global developmental delay; Motor delay; Seizures; High palate; Abnormal facial shape; Abnormality of the pinna; Generalized tonic-clonic seizures; Prominent forehead; Limb tremor 2017-01-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000255688 SCV000708615 pathogenic not provided 2017-06-07 criteria provided, single submitter clinical testing
GeneDx RCV000255688 SCV000321575 pathogenic not provided 2017-12-07 criteria provided, single submitter clinical testing The R108W variant in the EARS2 gene has been reported previously in association with leukoencephalopathy with thalamus and brainstem involvement (LTBL) in several unrelated individuals who were homozygous for R108W or compound heterozygous for R108W and another pathogenic variant in the EARS2 gene (Steenweg et al., 2012; Taylor et al., 2014; Taskin et al., 2016). The R108W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R108W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Although this substitution occurs at a position that is not conserved, in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, we interpret R108W as a pathogenic variant.
GenomeConnect, ClinGen RCV000033009 SCV000606964 not provided Combined oxidative phosphorylation deficiency 12 no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
OMIM RCV000033009 SCV000056789 pathogenic Combined oxidative phosphorylation deficiency 12 2012-05-01 no assertion criteria provided literature only

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