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

gnomAD frequency: 0.00001  dbSNP: rs752742151

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000196053	SCV000251112	uncertain significance	not provided	2024-11-12	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31178897, 34416374, 32376792)
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 from Uncertain Significance to Uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001071849	SCV001237177	uncertain significance	Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency	2024-02-24	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 151 of the AIFM1 protein (p.Arg151Gln). This variant is present in population databases (rs752742151, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of AIFM1-related conditions and/or deafness (PMID: 31178897, 32376792, 34416374). ClinVar contains an entry for this variant (Variation ID: 214082). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AIFM1 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.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000768430	SCV001440835	uncertain significance	Severe X-linked mitochondrial encephalomyopathy	2023-05-26	criteria provided, single submitter	clinical testing	Criteria applied: PS4_SUP,PM2_SUP,PP3,BP5
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768430	SCV000899188	likely pathogenic	Severe X-linked mitochondrial encephalomyopathy		no assertion criteria provided	case-control