ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.427del (p.Val143fs)

dbSNP: rs766914147
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova RCV000677561 SCV000803074 pathogenic Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation Frameshift variant(PVS1); In vitro functional studies supportive of a damaging effect on the gene product (demonstrated nonsense mediated RNA decay; PS3); Very low frequency in ExAc (PM2)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779748 SCV000916523 pathogenic Metachromatic leukodystrophy 2017-12-04 criteria provided, single submitter clinical testing Variant summary: The ARSB c.427delG (p.Val143SerfsX41) variant results in a premature termination codon, predicted to cause a truncated or absent ARSB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 6/277178 control chromosomes at a frequency of 0.0000216, which does not exceed the estimated maximal expected allele frequency of a pathogenic ARSB variant (0.0022361). The variant has been reported in numerous affected individuals in the literature. Taken together, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000677561 SCV001579935 pathogenic Mucopolysaccharidosis type 6 2023-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val143Serfs*41) in the ARSB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSB are known to be pathogenic (PMID: 17458871, 22133300). This variant is present in population databases (rs766914147, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with mucopolysaccharidosis type VI (PMID: 14974081, 16435196, 17643332). ClinVar contains an entry for this variant (Variation ID: 559782). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000677561 SCV002518524 pathogenic Mucopolysaccharidosis type 6 2022-05-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV000677561 SCV004209280 pathogenic Mucopolysaccharidosis type 6 2024-03-16 criteria provided, single submitter clinical testing
Natera, Inc. RCV000677561 SCV001457629 pathogenic Mucopolysaccharidosis type 6 2020-09-16 no assertion criteria provided clinical testing

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