ClinVar Miner

Submissions for variant NM_006096.4(NDRG1):c.122A>G (p.His41Arg)

gnomAD frequency: 0.00054  dbSNP: rs2233318
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766501 SCV000292636 uncertain significance not provided 2019-08-30 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Listed as a variant int he NCBI SNP database; however, this variant was not found in this study and no additional information was provided (Hunter et al., 2003); This variant is associated with the following publications: (PMID: 12872253, 32376792)
Athena Diagnostics RCV000236642 SCV000614151 uncertain significance not specified 2016-10-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000551572 SCV000657840 uncertain significance Charcot-Marie-Tooth disease type 4 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 41 of the NDRG1 protein (p.His41Arg). This variant is present in population databases (rs2233318, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NDRG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 245649). 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) performed at Invitae indicates that this missense variant is not expected to disrupt NDRG1 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.
CeGaT Center for Human Genetics Tuebingen RCV000766501 SCV001155492 uncertain significance not provided 2018-04-01 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173707 SCV001336821 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Ambry Genetics RCV002365224 SCV002665054 uncertain significance Inborn genetic diseases 2022-07-19 criteria provided, single submitter clinical testing The p.H41R variant (also known as c.122A>G), located in coding exon 3 of the NDRG1 gene, results from an A to G substitution at nucleotide position 122. The histidine at codon 41 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001833250 SCV002815076 uncertain significance Charcot-Marie-Tooth disease type 4D 2022-05-18 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000766501 SCV004224220 uncertain significance not provided 2022-05-04 criteria provided, single submitter clinical testing BP4
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001833250 SCV005877010 uncertain significance Charcot-Marie-Tooth disease type 4D 2024-07-09 criteria provided, single submitter clinical testing The NDRG1 c.122A>G; p.His41Arg variant (rs2233318), is reported in the literature in an individual with symptoms of Charcot-Marie-Tooth disease (Volodarsky 2021). This variant is also reported in ClinVar (Variation ID: 245649) and is found in the South Asian population with an overall allele frequency of 0.1796% (55/30,616 alleles) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is neutral (REVEL: 0.128). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Volodarsky M et al. Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients. J Med Genet. 2021 Apr;58(4):284-288. PMID: 32376792.
Natera, Inc. RCV001833250 SCV002080815 uncertain significance Charcot-Marie-Tooth disease type 4D 2020-01-16 no assertion criteria provided clinical testing

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