Submissions for variant NM_058216.3(RAD51C):c.785_786insTTTTTTTTTTTTTTTTTTNNNNNNNNNNTCACCGTTTTAGCCGGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCCGTACTCGGTTATT (p.Leu262delinsPhePhePhePhePhePheXaaXaaXaaXaaSerProPheTer)

dbSNP: rs2143852568

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001924259	SCV002200400	pathogenic	Fanconi anemia complementation group O	2021-04-21	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with RAD51C-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 5 of the RAD51C gene (c.785_786ins?), causing a frameshift at codon 262 (p.Leu262fs). 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. 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. For these reasons, this variant has been classified as Pathogenic. 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 RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917).