Submissions for variant NM_182931.3(KMT2E):c.4040C>G (p.Thr1347Ser)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002933347	SCV003265509	benign	not provided	2023-11-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526948	SCV005040311	uncertain significance	not specified	2024-03-29	criteria provided, single submitter	clinical testing	Variant summary: KMT2E c.4040C>G (p.Thr1347Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251260 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4040C>G in individuals affected with O'Donnell-Luria-Rodan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2055468). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV004983198	SCV005613722	uncertain significance	Inborn genetic diseases	2024-09-27	criteria provided, single submitter	clinical testing	The c.4040C>G (p.T1347S) alteration is located in exon 26 (coding exon 24) of the KMT2E gene. This alteration results from a C to G substitution at nucleotide position 4040, causing the threonine (T) at amino acid position 1347 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.