Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Pediatric Genomic Medicine, |
RCV000196053 | SCV000510611 | uncertain significance | not provided | 2016-10-24 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
Invitae | RCV001071849 | SCV001237177 | uncertain significance | Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency | 2019-12-13 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AIFM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 214082). This variant is present in population databases (rs752742151, ExAC 0.01%). This sequence change replaces arginine with glutamine at codon 151 of the AIFM1 protein (p.Arg151Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. |
Institute of Human Genetics, |
RCV000768430 | SCV001440835 | uncertain significance | Severe X-linked mitochondrial encephalomyopathy | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000196053 | SCV000251112 | likely pathogenic | not provided | 2012-09-11 | flagged submission | clinical testing | p.Arg151Gln (CGG>CAG):c.452 G>A in exon 4 of the AIFM1 gene (NM_004208.3). The R151Q missense change likely associated with a mitochondrial disorder was identified in the AIFM1 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. Furthermore, the NHLBI ESP Exome Variant Server reports R151Q in the AIFM1 gene was not observed in approximately 3,200 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations, and R151Q was also not reported in the 1000 Genomes database. The amino acid change is non-conservative in that a positively charged Arginine residue is replaced by an uncharged Glutamine residue. This change occurs at a highly conserved position in the AIFM1 protein, and multiple in-silico analysis programs predict that R151Q is damaging to the AIFM1 protein. Therefore, R151Q is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s). |
Biochemistry Laboratory of CDMU, |
RCV000768430 | SCV000899188 | likely pathogenic | Severe X-linked mitochondrial encephalomyopathy | no assertion criteria provided | case-control |