Submissions for variant NM_014727.3(KMT2B):c.4199G>A (p.Arg1400His)

gnomAD frequency: 0.00001  dbSNP: rs371324331

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001354899	SCV004145473	uncertain significance	not provided	2023-01-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001354899	SCV004285175	benign	not provided	2023-11-14	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354899	SCV001549621	uncertain significance	not provided		no assertion criteria provided	clinical testing	The KMT2B p.Arg1400His variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs371324331) and was identified in control databases in 2 of 239032 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 15024 chromosomes (freq: 0.000067) and European (non-Finnish) in 1 of 106468 chromosomes (freq: 0.000009), while the variant was not observed in the Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Arg1400 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.