Submissions for variant NM_021074.5(NDUFV2):c.17C>G (p.Ala6Gly)

dbSNP: rs559485096

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000401738	SCV000410196	uncertain significance	Mitochondrial complex I deficiency, nuclear type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Baylor Genetics	RCV001329208	SCV001520583	uncertain significance	Mitochondrial complex 1 deficiency, nuclear type 7	2019-12-16	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV001545608	SCV001764975	likely benign	not provided	2019-09-03	criteria provided, single submitter	clinical testing
Invitae	RCV001545608	SCV002316457	uncertain significance	not provided	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 6 of the NDUFV2 protein (p.Ala6Gly). This variant is present in population databases (rs559485096, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with NDUFV2-related conditions. ClinVar contains an entry for this variant (Variation ID: 327876). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.