Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000868580 | SCV001009925 | benign | Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency | 2024-02-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002051816 | SCV002319081 | uncertain significance | not provided | 2024-09-25 | criteria provided, single submitter | clinical testing | Identified as heterozygous in several unrelated Chinese females with bilateral auditory neuropathy in published literature, and in one female with unilateral auditory neuropathy, suggesting possible X-linked dominant inheritance (PMID: 34175691, 32684920); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in 37/14851 (0.2491%) alleles from individuals of East Asian background in large population cohorts (gnomAD); unknown if this represents a pathogenic founder variant or a common benign variant in this population; This variant is associated with the following publications: (PMID: 31832524, Chai_2021_Editorial, 34175691, 32684920, 25986071, 35578252) |
| ARUP Laboratories, |
RCV002051816 | SCV005878152 | uncertain significance | not provided | 2024-04-16 | criteria provided, single submitter | clinical testing | The AIFM1 c.1030C>T; p.Leu344Phe variant (rs184474885, ClinVar Variation ID: 162477) is reported in the literature in individuals affected with auditory neuropathy, including affected heterozygous female patients (Song 2021, Wang 2020, Zong 2015). Additionally, this variant was found in an individual affected with Charcot-Marie-Tooth disease-4 (Chen 2022), and in an infant with focal seizures (Ma 2019). This variant is found in the East Asian population with an allele frequency of 0.25% (37/14,851 alleles, including 20 hemizygotes) in the Genome Aggregation Database (v2.1.1). Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.279). Due to conflicting information, the clinical significance of this variant is uncertain at this time. References: Chen J et al. Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations. BMC Neurol. 2022 May 16;22(1):180. PMID: 35578252. Ma X et al. Genetic diagnosis of neonatal-onset seizures. Genes Dis. 2019 Feb 8;6(4):441-447. PMID: 31832524. Song M et al. Clinical characteristics of patients with unilateral auditory neuropathy. Am J Otolaryngol. 2021 Sep-Oct;42(5):103143. PMID: 34175691. Wang H et al. High Frequency of AIFM1 Variants and Phenotype Progression of Auditory Neuropathy in a Chinese Population. Neural Plast. 2020 Jul 1;2020:5625768. PMID: 32684920. Zong L et al. Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder. J Med Genet. 2015 Aug;52(8):523-31. PMID: 25986071. |
| Deafness Gene Diagnosis, |
RCV000149862 | SCV000196716 | likely pathogenic | Deafness, X-linked 5 | no assertion criteria provided | clinical testing | ||
| OMIM | RCV000149862 | SCV000257353 | pathogenic | Deafness, X-linked 5 | 2015-08-01 | no assertion criteria provided | literature only |