Submissions for variant NM_020247.5(COQ8A):c.1665G>A (p.Met555Ile)

gnomAD frequency: 0.00016  dbSNP: rs199874519

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000210698	SCV000262917	likely pathogenic	Inborn genetic diseases	2014-02-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000482785	SCV000569988	likely pathogenic	not provided	2023-12-04	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: 25356970, 25280894, 32337771, 25131622)
Illumina Laboratory Services, Illumina	RCV000778972	SCV000915400	likely pathogenic	Autosomal recessive ataxia due to ubiquinone deficiency	2024-09-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000482785	SCV001250074	likely pathogenic	not provided	2021-03-01	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000482785	SCV002771189	likely pathogenic	not provided	2022-06-30	criteria provided, single submitter	clinical testing	The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant appears to be associated with disease in at least one family. Computational tools predict that this variant is damaging.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000482785	SCV003524095	pathogenic	not provided	2023-10-23	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 555 of the COQ8A protein (p.Met555Ile). This variant is present in population databases (rs199874519, gnomAD 0.07%). This missense change has been observed in individuals with clinical features of coenzyme Q10 deficiency (PMID: 25131622, 32337771). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 225030). 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 expected to disrupt COQ8A protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000778972	SCV004041767	likely pathogenic	Autosomal recessive ataxia due to ubiquinone deficiency	2023-10-09	no assertion criteria provided	clinical testing
Solve-RD Consortium	RCV000778972	SCV005091416	likely pathogenic	Autosomal recessive ataxia due to ubiquinone deficiency	2022-06-01	no assertion criteria provided	provider interpretation	Variant confirmed as disease-causing by referring clinical team