Submissions for variant NM_020381.4(PDSS2):c.667G>A (p.Val223Ile)

gnomAD frequency: 0.00130  dbSNP: rs35555197

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000677022	SCV000252088	uncertain significance	not provided	2024-08-06	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV000765862	SCV000897258	uncertain significance	Coenzyme Q10 deficiency, primary, 3	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000677022	SCV001120828	likely benign	not provided	2024-01-22	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294075	SCV002587475	uncertain significance	Kidney disorder	2016-12-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003323448	SCV004029604	uncertain significance	not specified	2023-07-21	criteria provided, single submitter	clinical testing	Variant summary: PDSS2 c.667G>A (p.Val223Ile) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0013 in 246528 control chromosomes (gnomAD). To our knowledge, no occurrence of c.667G>A in individuals affected with Coenzyme Q10 Deficiency, Primary, 3 and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=4) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV000677022	SCV004032692	uncertain significance	not provided	2024-06-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000765862	SCV004040694	uncertain significance	Coenzyme Q10 deficiency, primary, 3	2023-07-17	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000677022	SCV000802855	uncertain significance	not provided	2018-01-11	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003937738	SCV004750492	likely benign	PDSS2-related disorder	2021-07-13	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).