ClinVar Miner

Submissions for variant NM_152419.3(HGSNAT):c.1345dup (p.Asp449fs) (rs483352894)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000001290 SCV000474016 uncertain significance Mucopolysaccharidosis, MPS-III-C 2017-04-27 criteria provided, single submitter clinical testing The HGSNAT c.1345dupG (p.Asp449GlyfsTer21) variant results in a frameshift and is expected to result in premature premature truncation of the protein. Fan et al. (2006) reported this variant in a compound heterozygous state with a splicing variant in one of two cell lines from individuals with mucopolysaccharidosis type III-C. The p.Asp449GlyfsTer21 variant is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium. This frequency is based on one allele in a region of good sequencing coverage, so the variant is presumed to be rare. Based on the limited evidence and the potential impact of frameshift variants, the p.Asp449GlyfsTer21 variant is classified as a variant of unknown significance but suspicious for pathogenicity for mucopolysaccharidosis type III. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000001290 SCV000784408 pathogenic Mucopolysaccharidosis, MPS-III-C 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000662072 SCV000784409 pathogenic Retinitis pigmentosa 73 2018-03-05 criteria provided, single submitter clinical testing
Invitae RCV001390806 SCV001592654 pathogenic Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 2020-04-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp449Glyfs*21) in the HGSNAT gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs483352894, ExAC 0.002%). This variant has been observed in individual(s) with mucopolysaccharidosis type IIIC (PMID: 16960811, 19479962, 31228227). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1231). Loss-of-function variants in HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001290 SCV000021440 pathogenic Mucopolysaccharidosis, MPS-III-C 2006-10-01 no assertion criteria provided literature only

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