Submissions for variant NM_182931.3(KMT2E):c.5555dup (p.Tyr1852Ter)

dbSNP: rs1799414845

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002863211	SCV003229978	likely benign	not provided	2024-06-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003418621	SCV004106805	uncertain significance	KMT2E-related disorder	2023-07-22	criteria provided, single submitter	clinical testing	The KMT2E c.5555dupA variant is predicted to result in premature protein termination (p.Tyr1852*). This variant is located in the terminal exon and may not undergo nonsense-mediated mRNA decay. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics	RCV004064991	SCV004896655	uncertain significance	Inborn genetic diseases	2024-01-23	criteria provided, single submitter	clinical testing	The c.5555dupA (p.Y1852*) alteration, located in exon 27 (coding exon 25) of the KMT2E gene, consists of a duplication of A at position 5555, causing a translational frameshift with a predicted alternate stop codon after amino acids. This alteration occurs at the 3' terminus of the KMT2E gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last seven amino acids of the protein. The exact functional effect of this alteration is unknown. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.