Submissions for variant NM_006096.4(NDRG1):c.1081C>T (p.Arg361Cys)

gnomAD frequency: 0.00002  dbSNP: rs779065972

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235589	SCV000294186	uncertain significance	not provided	2016-05-24	criteria provided, single submitter	clinical testing	The R361C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R361C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197027	SCV001367662	uncertain significance	Charcot-Marie-Tooth disease type 4D	2018-11-08	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001854879	SCV002151394	uncertain significance	Charcot-Marie-Tooth disease type 4	2022-03-03	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 361 of the NDRG1 protein (p.Arg361Cys). This variant is present in population databases (rs779065972, gnomAD 0.004%). 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: 246590). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics	RCV002429157	SCV002730272	uncertain significance	Inborn genetic diseases	2021-06-12	criteria provided, single submitter	clinical testing	The p.R361C variant (also known as c.1081C>T), located in coding exon 15 of the NDRG1 gene, results from a C to T substitution at nucleotide position 1081. The arginine at codon 361 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV000235589	SCV005409513	uncertain significance	not provided	2024-06-18	criteria provided, single submitter	clinical testing	BP4
Natera, Inc.	RCV001197027	SCV002085018	uncertain significance	Charcot-Marie-Tooth disease type 4D	2021-01-21	no assertion criteria provided	clinical testing