ClinVar Miner

Submissions for variant NM_024312.5(GNPTAB):c.569A>T (p.Asp190Val) (rs34946266)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632919 SCV000754124 uncertain significance Mucolipidosis type II; Pseudo-Hurler polydystrophy 2017-11-27 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 190 of the GNPTAB protein (p.Asp190Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is present in population databases (rs34946266, ExAC 0.002%). This variant has been reported in combination with a different GNPTAB variant in individuals affected with mucolipidoses (PMID: 16465621). ClinVar contains an entry for this variant (Variation ID: 38431). This variant is also known as c.733A>G (D190V) in the literature. Experimental studies have shown that this variant has a minimal impact on enzyme activity in vitro, however, in patient fibroblasts or lymphoblasts, this variant is associated with aberrant RNA splicing and reduced enzyme activity (PMID: 16465621, 25505245). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV001729354 SCV001976655 likely pathogenic Mucolipidosis type II 2021-10-01 criteria provided, single submitter clinical testing PM2, PP2, PP3, PP4, PP5
GeneReviews RCV000031988 SCV000054689 pathologic Mucopolysaccharidosis, MPS-III-A 2012-05-10 no assertion criteria provided curation Converted during submission to Pathogenic.

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