Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002323874 | SCV002607623 | likely pathogenic | Cardiovascular phenotype | 2021-04-29 | criteria provided, single submitter | clinical testing | The c.313+4_313+16del13 intronic variant, located in intron 3 of the LDLR gene, results from a deletion of 13 nucleotides within intron 3 of the LDLR gene. This variant has been reported in one individual with familial hypercholesterolemia (FH); however, clinical details were limited (Pirillo A et al. Atheroscler Suppl, 2017 Oct;29:17-24). Additional alterations impacting the same donor site (c.313+2dupT; c.313+5G>A; c.313+6T>C) have been detected in individuals with FH, and RNA studies have demonstrated skipping of exon 3 (Liguori R et al. Hum. Mutat., 2001 May;17:433; Bourbon M et al. J. Med. Genet., 2009 May;46:352-7; Sánchez-Hernández RM et al. Circ Cardiovasc Genet, 2016 Dec;9:504-510; Etxebarria A et al. Hum. Mutat., 2012 Jan;33:232-43). This nucleotide region is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000508810 | SCV000606078 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |