ClinVar Miner

Submissions for variant NM_152464.3(VMA12):c.92G>C (p.Arg31Pro)

gnomAD frequency: 0.00006  dbSNP: rs782531869
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002517364 SCV003253251 pathogenic not provided 2023-08-04 criteria provided, single submitter clinical testing Studies have shown that this missense change alters TMEM199 gene expression (PMID: 29321044). For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 218964). This missense change has been observed in individual(s) with congenital disorder of glycosylation type II (PMID: 26833330, 29321044). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs782531869, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 31 of the TMEM199 protein (p.Arg31Pro).
PreventionGenetics, part of Exact Sciences RCV003407721 SCV004114709 likely pathogenic TMEM199-related disorder 2023-08-12 criteria provided, single submitter clinical testing The TMEM199 c.92G>C variant is predicted to result in the amino acid substitution p.Arg31Pro. This variant has been reported in the homozygous and compound heterozygous states in patients with abnormal protein glycosylation (Jansen et al. 2016. PubMed ID: 26833330; Vajro et al. 2018. PubMed ID: 29321044). This variant is reported in 0.0087% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-26684785-G-C). This variant is interpreted as likely pathogenic.
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center RCV000210790 SCV000257475 pathogenic Congenital disorders of glycosylation type II no assertion criteria provided research
OMIM RCV000208697 SCV000264469 pathogenic TMEM199-CDG 2016-02-29 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.