Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002551546 | SCV001588184 | pathogenic | not provided | 2018-03-05 | criteria provided, single submitter | clinical testing | This sequence change is an Alu-mediated insertion in exon 5 of the FH mRNA (c.603_604insAlu), causing a frameshift at codon 201 (p.Ile201fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in FH are known to be pathogenic (PMID: 11865300, 21398687). For these reasons, this variant has been classified as Pathogenic. |
Labcorp Genetics |
RCV001385997 | SCV001586065 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2018-02-27 | flagged submission | clinical testing | This sequence change is an Alu-mediated insertion in exon 6 of the ACVRL1 mRNA (c.684_685insAlu), causing a frameshift at codon 229 (p.Lys229fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). For these reasons, this variant has been classified as Pathogenic. |