Submissions for variant NM_000404.4(GLB1):c.1310A>G (p.Asn437Ser)

dbSNP: rs202237232

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000669669	SCV000794445	likely benign	GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis	2017-09-29	criteria provided, single submitter	clinical testing
Invitae	RCV000874342	SCV001016502	likely benign	Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001150120	SCV001311133	uncertain significance	GM1 gangliosidosis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001150121	SCV001311134	uncertain significance	Mucopolysaccharidosis, MPS-IV-B	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002222593	SCV002500768	benign	not specified	2022-03-03	criteria provided, single submitter	clinical testing	Variant summary: GLB1 c.1310A>G (p.Asn437Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0025 in 151860 control chromosomes, predominantly at a frequency of 0.0085 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes (gnomAD v3.1). The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 9-fold of the estimated maximal expected allele frequency for a pathogenic variant in GLB1 causing Mucopolysaccharidosis Type IVB (Morquio Syndrome B) phenotype (0.00091), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1310A>G in individuals affected with Mucopolysaccharidosis Type IVB (Morquio Syndrome B) and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign (n=2) or VUS (n=1). Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV003928160	SCV004738341	likely benign	GLB1-related condition	2021-07-28	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).