ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.458T>C (p.Ile153Thr) (rs150577656)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409634 SCV000486977 likely pathogenic Congenital disorder of glycosylation, type Ia 2016-09-14 criteria provided, single submitter clinical testing
Invitae RCV000409634 SCV000960841 likely pathogenic Congenital disorder of glycosylation, type Ia 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 153 of the PMM2 protein (p.Ile153Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs150577656, ExAC 0.002%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with congenital disorder of glycosylation (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has been observed in combination with another PMM2 variant in individuals affected with congenital disorder of glycosylation, type Ia (PMID: 11156536, 25497157, 26502900, 11058895). ClinVar contains an entry for this variant (Variation ID: 371406). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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