Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016937 | SCV001177946 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-12-21 | criteria provided, single submitter | clinical testing | The c.291_296delCTACCC variant (also known as p.Y98_P99del) is located in coding exon 1 of the VHL gene. This variant results from an in-frame CTACCC deletion at nucleotide positions 291 to 296. This results in the in-frame deletion of two amino acids (YP) at codons 98 to 99. An additional missense alteration at one of the deleted codons, p.Y98H, has been reported in multiple Von Hippel-Lindau families in the literature (Boedeker CC et al. J Clin Endocrinol Metab. 2009;94(6):1938-44; Gallou C et al. Hum. Mutat., 2004 Sep;24:215-24; Nielsen SM et al. Am. J. Med. Genet. A, 2011 Jan;155A:168-73). Internal structural analysis of the c.291_296delCTACCC variant suggests that it results in the elimination of specific interactions with HIF1α and impairs HIF1α binding (Min JH et al. Science, 2002 Jun;296:1886-9; Van Molle I et al. Chem. Biol., 2012 Oct;19:1300-12). The deleted amino acid region is well conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |