Submissions for variant NM_006096.3(NDRG1):c.31G>A (p.Ala11Thr) (rs145871479)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001083085	SCV000261903	likely benign	Charcot-Marie-Tooth disease type 4	2020-12-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000710163	SCV000292635	likely benign	not provided	2021-03-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32376792)
Athena Diagnostics Inc	RCV000710163	SCV000614152	likely benign	not provided	2019-11-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV000710163	SCV000884217	uncertain significance	not provided	2017-06-14	criteria provided, single submitter	clinical testing	The p.Ala11Thr variant (rs145871479) has not been reported in the medical literature; however, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 220934). It is listed in the Genome Aggregation Database (gnomAD) browser with an overall frequency of 0.11% (identified in 309 out of 277,200 chromosomes, including 1 homozygote). The alanine at codon 111 is only moderately conserved considering 15 species (Alamut software v2.9), and computational analyses suggest this variant does not have a significant effect on NDRG1 protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: polymorphism). However, based on the available information, the clinical significance of the p.Ala11Thr variant cannot be determined with certainty.
Illumina Clinical Services Laboratory,Illumina	RCV001162095	SCV001324030	uncertain significance	Charcot-Marie-Tooth disease, type 4D	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173729	SCV001336843	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000710163	SCV001500524	uncertain significance	not provided	2020-11-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000710163	SCV001716005	uncertain significance	not provided	2020-07-16	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001083085	SCV001456524	likely benign	Charcot-Marie-Tooth disease type 4	2019-12-27	no assertion criteria provided	clinical testing