ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.495_497del (p.Leu166del) (rs754077128)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics 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 2019-05-16 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, ExAC 0.1%). This variant has been observed in several individuals affected with GM1-gangliosidosis (PMID: 20920281, 30267299). This variant has been reported to affect GLB1 protein function (PMID: 20920281). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV001585790 SCV001821207 pathogenic Infantile GM1 gangliosidosis 2021-04-19 no assertion criteria provided literature only High prevalence in Chinese population; associated with GM1 infantile and late-infantile form

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