Submissions for variant NM_007103.4(NDUFV1):c.1378C>T (p.Arg460Trp)

gnomAD frequency: 0.00009  dbSNP: rs372047256

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000303945	SCV000373648	uncertain significance	Leigh syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000342474	SCV000373649	uncertain significance	Mitochondrial complex I deficiency	2016-06-14	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001196497	SCV001367105	uncertain significance	Mitochondrial complex 1 deficiency, nuclear type 4	2019-03-01	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: No criteria apply.
Baylor Genetics	RCV001333610	SCV001526250	uncertain significance	Mitochondrial complex I deficiency, nuclear type 1	2018-05-24	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	RCV001859819	SCV002157600	uncertain significance	not provided	2022-02-18	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 460 of the NDUFV1 protein (p.Arg460Trp). This variant is present in population databases (rs372047256, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NDUFV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 305758). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The tryptophan 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	RCV003165831	SCV003876894	uncertain significance	Inborn genetic diseases	2023-02-23	criteria provided, single submitter	clinical testing	The c.1378C>T (p.R460W) alteration is located in exon 10 (coding exon 10) of the NDUFV1 gene. This alteration results from a C to T substitution at nucleotide position 1378, causing the arginine (R) at amino acid position 460 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.