ClinVar Miner

Submissions for variant NM_000404.4(GLB1):c.145C>T (p.Arg49Cys) (rs72555358)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000175599 SCV000227114 uncertain significance not provided 2014-06-24 criteria provided, single submitter clinical testing
Counsyl RCV000672371 SCV000797470 likely pathogenic GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis 2018-01-25 criteria provided, single submitter clinical testing
Invitae RCV000707313 SCV000836403 uncertain significance Mucopolysaccharidosis, MPS-IV-B; GM1 gangliosidosis 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 49 of the GLB1 protein (p.Arg49Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs72555358, ExAC 0.009%). This variant has been observed in combination with a pathogenic GLB1 variant in an individual affected with GM1-gangliosidosis (PMID: 15365997) and as heterozygous (no second variant identified) in an individual with the same disease (PMID: 1909089). ClinVar contains an entry for this variant (Variation ID: 923). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The observation of one or more missense substitutions at this codon (p.Arg49Cys and p.Arg49His) in affected individuals suggests that this may be a clinically significant residue (PMID: 15365997, 15986423). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 923).
OMIM RCV000000971 SCV000021121 pathogenic Infantile GM1 gangliosidosis 1991-09-01 no assertion criteria provided literature only

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