Submissions for variant NM_000249.4(MLH1):c.545+19G>T

gnomAD frequency: 0.00007  dbSNP: rs41285099

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000157757	SCV000170287	benign	not specified	2014-03-28	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl	RCV000409249	SCV000489297	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2016-09-13	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000581128	SCV000684840	likely benign	Hereditary cancer-predisposing syndrome	2015-10-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000059816	SCV000696169	uncertain significance	not provided	2016-01-11	criteria provided, single submitter	clinical testing	Variant summary: The c.545+19G>T variant affects a non-conserved intronic nucleotide. One in-silico tool predicts benign outcome for this variant. 4/5 programs in Alamut predict that this variant does not affect normal splicing. However, these prediction are not confirmed by experimental studies. This variant is found in 4/121334 control chromosomes at a frequency of 0.000033, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0007105). One clinical laboratory classified this variant as benign, however, without evidence for independent review. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance - possibly benign variant until additional information becomes available.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002054916	SCV002423628	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000157757	SCV004243136	likely benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Narod's Lab, University of Toronto	RCV000059816	SCV000091386	not provided	not provided		no assertion provided	not provided