ClinVar Miner

Submissions for variant NM_000404.2(GLB1):c.464T>G (p.Leu155Arg) (rs376710410)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665871 SCV000790063 likely pathogenic GM1 gangliosidosis type 2; Gangliosidosis GM1 type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2017-03-02 criteria provided, single submitter clinical testing
Fulgent Genetics RCV000665871 SCV000894316 pathogenic GM1 gangliosidosis type 2; Gangliosidosis GM1 type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000256106 SCV000321730 pathogenic not provided 2016-04-19 criteria provided, single submitter clinical testing The L155R pathogenic variant in the GLB1 gene has been reported previously in the homozygous state in an individual with type III (adult) GM1-gangliosidosis (Santamaria et al., 2007). This variant was also reported in three other individuals with adult or late infantile GM1-gangliosidosis, each of whom also harbored a second GLB1 pathogenic variant, although the phase of the variants could not be confirmed, as parental testing was not performed (Hofer et al., 2009; Hofer et al., 2010). Functional studies demonstrate that the L155R variant reduces beta-galactosidase activity (Hofer et al., 2009). This variant was not observed at any significant frequency in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L155R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (D151Y, D151V) have been reported in the Human Gene Mutation Database in association with GM1-gangliosidosis (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret L155R as a pathogenic variant.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000256106 SCV000801392 likely pathogenic not provided 2017-05-31 no assertion criteria provided clinical testing

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