ClinVar Miner

Submissions for variant NM_014244.5(ADAMTS2):c.1906C>T (p.His636Tyr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002620885 SCV003511930 uncertain significance Ehlers-Danlos syndrome, dermatosparaxis type 2021-09-17 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 636 of the ADAMTS2 protein (p.His636Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs778646166, ExAC 0.2%). This variant has not been reported in the literature in individuals with ADAMTS2-related disease. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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