ClinVar Miner

Submissions for variant NM_139027.6(ADAMTS13):c.1423C>T (p.Pro475Ser)

gnomAD frequency: 0.00232  dbSNP: rs11575933
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000251648 SCV000315859 likely benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000006170 SCV000478321 likely benign Upshaw-Schulman syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000767050 SCV000617792 uncertain significance not provided 2021-04-21 criteria provided, single submitter clinical testing Often reported in the literature as a polymorphism with a suspected northeastern Asian origin of the variant (Nakagawa et al., 2016; Tso et al., 2020); Reported in a deceased female infant with diarrhea negative hemolytic uremic syndrome and ADAMTS13 activity that was 54% of normal levels (Choi et al., 2011); Published functional crystal structure studies demonstrate that the P475S mutant destabilizes the protein leading to reduced substrate affinity and moderately reduced catalytic efficiency of the ADAMTS13 enzyme (Akiyama et al., 2013); Published functional cell transfection studies demonstrate the P475S variant resulted in very low enzyme activity (Kokame et al., 2002); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in 2.024% (642/31714 alleles) individuals of Latino background and 1.524% (273/17908 alleles) individuals of East Asian background in the gnomAD dataset, including multiple unrelated homozygous individuals (Lek et al., 2016); This variant is associated with the following publications: (PMID: 12195022, 23715102, 19847791, 18665921, 27497325, 23621748, 22768050, 12181489, 21676167, 18581589, 21488199, 29669506, 29304523, 32588586)
Mendelics RCV000006170 SCV001137945 benign Upshaw-Schulman syndrome 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000767050 SCV003246220 benign not provided 2024-01-22 criteria provided, single submitter clinical testing
OMIM RCV000006170 SCV000026352 pathogenic Upshaw-Schulman syndrome 2002-09-03 no assertion criteria provided literature only

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