ClinVar Miner

Submissions for variant NM_000263.4(NAGLU):c.680A>C (p.His227Pro)

dbSNP: rs747155746
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668224 SCV000792792 uncertain significance Mucopolysaccharidosis, MPS-III-B 2017-07-14 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000996550 SCV001151312 likely pathogenic not provided 2019-11-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000668224 SCV004099538 likely pathogenic Mucopolysaccharidosis, MPS-III-B 2023-09-01 criteria provided, single submitter clinical testing Variant summary: NAGLU c.680A>C (p.His227Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251014 control chromosomes (gnomAD). c.680A>C has been reported in the literature as a compound heterozygous genotype in an individual affected with attenuated Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) (Weber_1999). Experimental evidence evaluating an impact on protein function in vitro found that the variant results in <10% of normal activity (Clark_2018). The following publications have been ascertained in the context of this evaluation (PMID: 29979746, 10094189). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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