ClinVar Miner

Submissions for variant NM_001303.4(COX10):c.1193G>A (p.Arg398His)

gnomAD frequency: 0.00007  dbSNP: rs200942884
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224667 SCV000280690 benign not provided 2015-05-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000224667 SCV002233654 uncertain significance not provided 2022-11-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 398 of the COX10 protein (p.Arg398His). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COX10 protein function. ClinVar contains an entry for this variant (Variation ID: 235251). This variant has not been reported in the literature in individuals affected with COX10-related conditions. This variant is present in population databases (rs200942884, gnomAD 0.02%).
GeneDx RCV000224667 SCV003194929 uncertain significance not provided 2023-01-20 criteria provided, single submitter clinical testing Reported as heterozygous with no second variant identified in an individual with intellectual disability who had a different genetic etiology for the phenotype (Celis et al., 2015); 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: 25758935)
Ambry Genetics RCV002516218 SCV003740232 uncertain significance Inborn genetic diseases 2022-07-29 criteria provided, single submitter clinical testing The c.1193G>A (p.R398H) alteration is located in exon 7 (coding exon 7) of the COX10 gene. This alteration results from a G to A substitution at nucleotide position 1193, causing the arginine (R) at amino acid position 398 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV000224667 SCV005412664 uncertain significance not provided 2024-05-09 criteria provided, single submitter clinical testing PP3, PM2
Fulgent Genetics, Fulgent Genetics RCV005008175 SCV005643755 uncertain significance Mitochondrial complex 4 deficiency, nuclear type 3 2024-01-22 criteria provided, single submitter clinical testing

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