ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.95_96delinsGC (p.Leu32Arg) (rs398123312)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169510 SCV000220979 likely pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2014-12-24 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000790826 SCV000227089 pathogenic not provided 2012-12-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000169510 SCV000696505 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2016-06-26 criteria provided, single submitter clinical testing Variant summary: The PMM2 c.95_96delinsGC (p.Leu32delinsArg) causes an in-frame deletion/insertion resulting in a missense change. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/106694, which does not exceed the estimated maximal expected allele frequency for a pathogenic PMM2 variant of 1/178 (0.0055902). The variant of interest has been observed in multiple affected individuals as a compound heterozygote via multiple publications. In addition, multiple functional studies show the variant to impede PMM2 wild type functions. Furthermore, multiple reputable databases/clinical laboratories cite the variant as "likely pathogenic/pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Pathogenic.
Invitae RCV000169510 SCV000944609 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2019-01-05 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 32 of the PMM2 protein (p.Leu32Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with PMM2-related conditions and observed segregating with this disease in families (PMID: 23988505, 17451957, 25355454, 19235233). ClinVar contains an entry for this variant (Variation ID: 92807). Experimental studies have shown that this missense change has a deleterious effect on protein function (PMID: 10922383, 11715002). For these reasons, this variant has been classified as Pathogenic.

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