ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.647A>T (p.Asn216Ile) (rs78290141)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724043 SCV000232514 pathogenic not provided 2014-07-17 criteria provided, single submitter clinical testing
Invitae RCV000008146 SCV000836724 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2018-05-09 criteria provided, single submitter clinical testing This sequence change replaces asparagine with isoleucine at codon 216 of the PMM2 protein (p.Asn216Ile). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individuals with low phosphomanomutase enzyme activity, findings that are highly specific for PMM2-CDG (CDG-Ia) (PMID: 9140401, 25355454). Additionally, this variant has been reported in as homozygous or in combination with another PMM2 variant in individuals affected with PMM2-congenital disorder of glycosylation (CDG-Ia) (PMID: 9140401, 9497260, 11875054, 25355454, 12905014, 12905014, 23430838). ClinVar contains an entry for this variant (Variation ID: 7707). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008146 SCV000028351 pathogenic Carbohydrate-deficient glycoprotein syndrome type I 2003-10-01 no assertion criteria provided literature only

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