Submissions for variant NM_001303.4(COX10):c.1027T>C (p.Cys343Arg)

gnomAD frequency: 0.00041  dbSNP: rs200818252

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000442977	SCV000511814	uncertain significance	not provided	2016-09-20	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV002480280	SCV000895071	uncertain significance	Mitochondrial complex 4 deficiency, nuclear type 3	2022-02-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001333919	SCV001526628	uncertain significance	Leigh syndrome	2018-09-27	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV000442977	SCV002127756	uncertain significance	not provided	2021-12-03	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 343 of the COX10 protein (p.Cys343Arg). This variant is present in population databases (rs200818252, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with COX10-related conditions. ClinVar contains an entry for this variant (Variation ID: 377357). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics	RCV002524739	SCV003588629	uncertain significance	Inborn genetic diseases	2022-06-13	criteria provided, single submitter	clinical testing	The c.1027T>C (p.C343R) alteration is located in exon 7 (coding exon 7) of the COX10 gene. This alteration results from a T to C substitution at nucleotide position 1027, causing the cysteine (C) at amino acid position 343 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV000442977	SCV004224315	uncertain significance	not provided	2023-04-03	criteria provided, single submitter	clinical testing	BP4, PM2
Baylor Genetics	RCV002480280	SCV005049307	uncertain significance	Mitochondrial complex 4 deficiency, nuclear type 3	2023-12-11	criteria provided, single submitter	clinical testing
Johnston Lab, North Central College	RCV000442977	SCV005200374	not provided	not provided		no assertion provided	in vitro