Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Foundation for Research in Genetics and Endocrinology, |
RCV000844877 | SCV000926257 | uncertain significance | GM1 gangliosidosis type 2 | 2019-05-07 | criteria provided, single submitter | clinical testing | Heterozygous variant c.495_497del (p.Leu166del) in exon-5 has been observed in GLB1 gene. The proband, born of a non-consanguineous marriage, presented with clinical indication of regression of milestones, moderate mental retardation, seizures, hypotonia and myoclonal jerks. MRI was suggestive of cerebral atrophy. The patient in our clinical analysis was diagnosed with the said variant in an autosomal recessive mode of inheritance. The variant is not reported in the 1000 genomes and ExAC databases. In silico prediction of the variant is probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. In summary, the said variant meets our criteria to be classified as uncertain significance based on the mode of inheritance, in silico prediction, allele frequency in population databases and lack of segregation study. |
Invitae | RCV001214281 | SCV001385956 | pathogenic | Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis | 2024-01-24 | criteria provided, single submitter | clinical testing | This variant, c.495_497del, results in the deletion of 1 amino acid(s) of the GLB1 protein (p.Leu166del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs754077128, gnomAD 0.06%). This variant has been observed in individual(s) with GM1-gangliosidosis (PMID: 20920281, 30267299). ClinVar contains an entry for this variant (Variation ID: 684406). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects GLB1 function (PMID: 20920281). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001585790 | SCV001821207 | not provided | Infantile GM1 gangliosidosis | no assertion provided | literature only | High prevalence in Chinese population; associated with GM1 infantile and late-infantile form |