Submissions for variant NM_000404.4(GLB1):c.1823T>C (p.Leu608Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004699771	SCV005204280	likely pathogenic	Mucopolysaccharidosis, MPS-IV-B	2024-06-13	criteria provided, single submitter	clinical testing	Variant summary: GLB1 c.1823T>C (p.Leu608Pro) results in a non-conservative amino acid change located in the Beta-galactosidase, galactose-binding domain (IPR048913) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249464 control chromosomes. c.1823T>C has been reported in the literature in individuals affected with Gm1-gangliosidosis (Higaki_2011). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results negligible enzyme activity when compared to wildtype (Higaki_2011). The following publication have been ascertained in the context of this evaluation (PMID: 21520340). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005023646	SCV005658078	likely pathogenic	GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis	2024-06-13	criteria provided, single submitter	clinical testing