ClinVar Miner

Submissions for variant NM_004208.4(AIFM1):c.452G>A (p.Arg151Gln)

gnomAD frequency: 0.00001  dbSNP: rs752742151
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics 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, University of Leipzig Medical Center RCV000768430 SCV001440835 uncertain significance Severe X-linked mitochondrial encephalomyopathy 2019-01-01 criteria provided, single submitter clinical testing
GeneDx 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, Chengde Medical University RCV000768430 SCV000899188 likely pathogenic Severe X-linked mitochondrial encephalomyopathy no assertion criteria provided case-control

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