ClinVar Miner

Submissions for variant NM_000902.4(MME):c.467del (p.Pro156fs) (rs749320057)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489776 SCV000577528 pathogenic not provided 2018-10-16 criteria provided, single submitter clinical testing The c.467delC variant in the MME gene has been reported previously to segregate with disease in two unrelated families with autosomal dominant late-onset peripheral neuropathy (Auer-Grumbach et al., 2016). Additionally, this variant was reported as homozygous in two mothers, and compound heterozygous with a MME nonsense variant in a third mother, all of whom had children with neonatal membranous glomerulopathy due to alloimmunization; presence or absence of neuropathy in these families was not noted (Debiec et al., 2004). The c.467delC variant causes a frameshift starting with codon Proline 156, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Pro156LeufsX14. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.467delC variant is observed in 25/34288 (0.07%) alleles from individuals of Latino background, and no individuals were reported to be homozygous (Lek et al., 2016). We interpret c.467delC as a pathogenic variant.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000489776 SCV001247099 pathogenic not provided 2019-12-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196532 SCV001367140 pathogenic Spinocerebellar ataxia 43 2019-11-14 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM1,PP5.
Invitae RCV000489776 SCV001412175 pathogenic not provided 2019-04-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro156Leufs*14) in the MME gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs749320057, ExAC 0.03%). This variant has been reported as heterozygous in individuals with late-onset axonal Charcot-Marie-Tooth disease (PMID: 27588448) and as homozygous or compound heterozygous in several mothers of children with alloimmune antenatal membranous nephropathy (PMID: 15464186, 25565308). It is also known as 466delC in the literature. ClinVar contains an entry for this variant (Variation ID: 426945). Loss-of-function variants in MME are known to be pathogenic (PMID: 26991897, 27588448). For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000489776 SCV001450210 likely pathogenic not provided 2017-06-30 criteria provided, single submitter clinical testing
OMIM RCV000255813 SCV000322710 risk factor Charcot-Marie-Tooth disease, axonal, type 2T 2016-10-06 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.