Submissions for variant NM_000530.8(MPZ):c.637G>C (p.Gly213Arg)

gnomAD frequency: 0.00005  dbSNP: rs202176679

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236004	SCV000294164	uncertain significance	not provided	2018-04-23	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the MPZ gene. The G213R variant has been reported previously in two siblings with axonal CMT; however, this variant was inherited from their unaffected father (Brozkova et al., 2010). The G213R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G213R 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. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Laboratory Services, Illumina	RCV001093884	SCV000350230	likely benign	Neuropathy, congenital hypomyelinating, 2	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000296319	SCV000350231	likely benign	Charcot-Marie-Tooth disease type 4E	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000373587	SCV000350232	likely benign	Roussy-Lévy syndrome	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000279139	SCV000350233	likely benign	Charcot-Marie-Tooth disease dominant intermediate D	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001093885	SCV000350234	likely benign	Charcot-Marie-Tooth disease type 1B	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000555621	SCV000636251	likely benign	Charcot-Marie-Tooth disease, type I	2024-12-12	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV000790309	SCV001337455	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001658084	SCV001880056	likely benign	not specified	2021-04-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365233	SCV002657895	likely benign	Inborn genetic diseases	2022-01-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000236004	SCV005434468	uncertain significance	not provided	2024-11-01	criteria provided, single submitter	clinical testing	MPZ: PM2:Supporting
Inherited Neuropathy Consortium	RCV000790309	SCV000929717	benign	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only