Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001377361 | SCV001574679 | likely pathogenic | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change affects codon 257 of the GNPTAB mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GNPTAB protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with mucolipidosis type III (PMID: 15633164). ClinVar contains an entry for this variant (Variation ID: 2761). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 7, but is expected to preserve the integrity of the reading-frame (PMID: 15633164). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001731275 | SCV001983660 | likely pathogenic | Mucolipidosis | 2021-09-13 | criteria provided, single submitter | clinical testing | Variant summary: GNPTAB c.771G>A (p.Leu257Leu) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant weakens a 5' donor site and one predicts the variant abolishes a 5' splicing donor site. Experimental evidence supports these predictions indicating that this variant affects mRNA splicing leading to the skipping of exon 7 (Steet_2005). The variant was absent in 251190 control chromosomes (gnomAD). c.771G>A has been reported in the literature in a homozygous individual affected with Mucolipidosis (Steet_2005). These data indicate that the variant may be associated with disease. Experimental evidence evaluating an impact on protein function demonstrated the variant results in the production of a minimal amount of functional enzyme (Steet_2005). A ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
OMIM | RCV000002888 | SCV000023046 | pathogenic | Mucolipidosis III alpha/beta, atypical | 2005-02-01 | no assertion criteria provided | literature only | |
Gene |
RCV000031990 | SCV000054691 | pathologic | Pseudo-Hurler polydystrophy | 2012-05-10 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
Natera, |
RCV001831508 | SCV002088602 | likely pathogenic | Mucolipidosis type II | 2020-07-21 | no assertion criteria provided | clinical testing |