ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.691G>A (p.Val231Met) (rs80338707)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000008158 SCV000678137 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2015-06-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000790822 SCV000232516 pathogenic not provided 2017-06-12 criteria provided, single submitter clinical testing
GeneReviews RCV000008158 SCV000040589 pathologic Carbohydrate-deficient glycoprotein syndrome type I 2011-04-21 no assertion criteria provided curation Converted during submission to Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000008158 SCV000696502 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2017-08-21 criteria provided, single submitter clinical testing Variant summary: The PMM2 c.691G>A (p.Val231Met) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 7/120856 control chromosomes at a frequency of 0.0000579, which does not exceed the estimated maximal expected allele frequency of a pathogenic PMM2 variant (0.0055902). This variant has been reported in many pts/families with evidence of co-segregation of the variant with disease. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000008158 SCV000633726 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2018-11-19 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 231 of the PMM2 protein (p.Val231Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs80338707, ExAC 0.01%). This variant has been reported in several individuals affected with PMM2-CDG, being one of the most common causes of the disease in European populations (PMID: 9497260, 10801058, 15844218, 23430838, 25355454). ClinVar contains an entry for this variant (Variation ID: 7719). Experimental studies have shown that this missense change reduces protein stability and function (PMID: 10386614). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008158 SCV000028363 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2000-08-01 no assertion criteria provided literature only

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