ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.710C>T (p.Thr237Met) (rs80338708)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623731 SCV000742595 pathogenic Inborn genetic diseases 2017-07-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514240 SCV000609595 pathogenic not provided 2017-08-24 criteria provided, single submitter clinical testing
Counsyl RCV000020237 SCV000221115 likely pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2015-02-06 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000514240 SCV000232513 pathogenic not provided 2017-05-13 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000020237 SCV000611239 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2017-05-18 criteria provided, single submitter clinical testing
GeneReviews RCV000020237 SCV000040590 pathologic Carbohydrate-deficient glycoprotein syndrome type I 2011-04-21 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000020237 SCV000757674 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2018-06-23 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 237 of the PMM2 protein (p.Thr237Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs80338708, ExAC 0.01%). This variant has been reported in combination with another PMM2 variant in individuals affected with congenital disorder of glycosylation type 1 (PMID: 11891694, 11589167, 23430838, 23988505, 21541725). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in one of these individuals which is consistent with autosomal recessive inheritance and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 21145). Experimental studies have shown that this missense change causes a significant reduction in PMM2 activity and destabilizes the protein (PMID: 21541725, 26014514). For these reasons, this variant has been classified as Pathogenic.

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