ClinVar Miner

Submissions for variant NM_019109.4(ALG1):c.826C>T (p.Arg276Trp) (rs151173406)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000023496 SCV000833498 likely pathogenic Congenital disorder of glycosylation type 1K 2018-05-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 276 of the ALG1 protein (p.Arg276Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs151173406, ExAC 0.01%). This variant has been reported in combination with another ALG1 variant in individuals affected with congenital disorder of glycosylation (PMID: 20679665, 26931382, Invitae), including individuals in whom this variant has been observed on the opposite chromosome (in trans) from a pathogenic variant. This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 30539). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
OMIM RCV000023496 SCV000044787 pathogenic Congenital disorder of glycosylation type 1K 2010-11-01 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics,University of Washington RCV000851250 SCV000993502 likely pathogenic Congenital disorder of glycosylation 2017-05-25 no assertion criteria provided research

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