ClinVar Miner

Submissions for variant NM_013339.4(ALG6):c.998C>T (p.Ala333Val) (rs121908443)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000005832 SCV000792595 pathogenic Congenital disorder of glycosylation type 1C 2017-07-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000005832 SCV000894082 pathogenic Congenital disorder of glycosylation type 1C 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000005832 SCV000915431 pathogenic Congenital disorder of glycosylation type 1C 2018-08-09 criteria provided, single submitter clinical testing The ALG6 c.998C>T (p.Ala333Val) missense variant is reported to be the most common cause of congenital disorders of glycosylation (CDG) (Drijvers et al. 2010; Ichikawa et al. 2013). Across a selection of the available literature, the p.Ala333Val variant has been reported in a total of eight individuals with CDG, including in four homozygotes, comprised of two sibling pairs who are cousins, and in four unrelated compound heterozygotes. This variant was also identified in a heterozygous state in five unaffected parents of the probands (Imbach et al. 1999; Westphal et al. 2000; Drijvers et al. 2010; Ichikawa et al. 2013; Dercksen et al. 2013). The p.Ala333Val variant was absent from controls but is reported at a frequency of 0.000075 in the European (non-Finnish) population of the Exome Aggregation Consortium. Functional studies in yeast with a hypoglycosylation phenotype showed that the p.Ala333Val variant was able to only partially restore glycosylation, whereas glycosylation was fully restored with the wild type protein (Imbach et al. 1999; Westphal et al. 2000). Based on the collective evidence, the p.Ala333Val variant is classified as pathogenic for congenital disorders of glycosylation. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000005832 SCV000026014 pathogenic Congenital disorder of glycosylation type 1C 1999-06-08 no assertion criteria provided literature only

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