ClinVar Miner

Submissions for variant NM_152464.3(TMEM199):c.92G>C (p.Arg31Pro)

gnomAD frequency: 0.00006  dbSNP: rs782531869
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002517364 SCV003253251 pathogenic not provided 2023-08-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Studies have shown that this missense change alters TMEM199 gene expression (PMID: 29321044). 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 condition 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

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