Submissions for variant NM_139027.6(ADAMTS13):c.3400+143del

dbSNP: rs1060499780

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000454327	SCV000538012	likely pathogenic	Upshaw-Schulman syndrome	2015-12-04	criteria provided, single submitter	clinical testing	The c.3541delG (p.Gln1183Argfs*43) frameshift variant in the ADAMTS13 gene is a novel variant and has not been previously reported. This c.3541delG variant is predicted to cause premature protein termination in exon 26 (out of a total of 29 exons in the coding sequence). Frameshift variants resulting in premature termination codons have been described in the ADAMTS13 gene in several affected individuals, including a single base-pair duplication of thymine (T) (c.3770dupT) (exon 27) (Levi et al., 2001) as well as a duplication of adenine (A), c.4143dupA (exon 29) (Schneppenheim et al., 2003) that are both predicted to result in protein truncation further down-stream from c.3541delG. This suggests that loss of function is a mechanism of disease. The c.3541delG variant has not been reported in the three control population databases (Exome Sequencing Project [ESP], 1000 Genomes, and ExAC). Therefore, this collective evidence supports the classification of the c.3541delG (p.Gln1183Argfs*43) as a recessive likely pathogenic variant for congenital TPP.