Submissions for variant NM_006785.4(MALT1):c.1661_1662insTTTTTTTTTTTTTTTTTNNNNNNNNNNGGCAGGGAGGTTGCAGTGAGCCGAGATGGCAGCAGTACAGTCCAGCTTCGGCTCCGCATGAGAGGGAGACCGTGGGGAGAGGGAGACAGAGCTCGAAGTAGTTT (p.Leu554delinsPhePhePhePhePhePheXaaXaaXaaXaaAlaGlyArgLeuGlnTer)

dbSNP: rs2144484668

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001956376	SCV002245806	pathogenic	Combined immunodeficiency due to MALT1 deficiency	2021-04-22	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 14 of the MALT1 gene (c.1661_1662ins?), causing a frameshift at codon 554 (p.Leu554fs). 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). This variant has not been reported in the literature in individuals with MALT1-related conditions. 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 MALT1 are known to be pathogenic (PMID: 23727036, 25627829). For these reasons, this variant has been classified as Pathogenic.