ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.1479G>T (p.Lys493Asn) (rs1172435886)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000810175 SCV000950366 uncertain significance Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2018-12-19 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 493 of the GLB1 protein (p.Lys493Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant also falls at the last nucleotide of exon 14 of the GLB1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with GM1 gangliosidosis type II (PMID: 25936995). 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 C0"). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
GenomeConnect - GM1 RCV000810175 SCV001338918 not provided Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 12-19-2018 by Lab or GTR ID 500031. GenomeConnect-GM1 assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant.

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