ClinVar Miner

Submissions for variant NM_016013.4(NDUFAF1):c.199G>A (p.Val67Ile)

gnomAD frequency: 0.00004  dbSNP: rs201452351
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001900007 SCV002123912 uncertain significance not provided 2022-04-30 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 67 of the NDUFAF1 protein (p.Val67Ile). This variant is present in population databases (rs201452351, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with NDUFAF1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002272508 SCV002557264 uncertain significance Mitochondrial complex 1 deficiency, nuclear type 11 2022-02-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with mitochondrial complex I deficiency, nuclear type 11 (MIM#618234). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from valine to isoleucine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 23 heterozygotes, 0 homozygotes). (SP) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Ambry Genetics RCV004039790 SCV003690130 uncertain significance not specified 2022-06-30 criteria provided, single submitter clinical testing The c.199G>A (p.V67I) alteration is located in exon 2 (coding exon 1) of the NDUFAF1 gene. This alteration results from a G to A substitution at nucleotide position 199, causing the valine (V) at amino acid position 67 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV002272508 SCV004236815 uncertain significance Mitochondrial complex 1 deficiency, nuclear type 11 2023-11-01 criteria provided, single submitter clinical testing

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