Submissions for variant NM_000249.4(MLH1):c.2080G>T (p.Glu694Ter)

gnomAD frequency: 0.00001  dbSNP: rs147542208

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV001784646	SCV002017490	pathogenic	not provided	2023-07-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002418578	SCV002727779	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-15	criteria provided, single submitter	clinical testing	The p.E694* pathogenic mutation (also known as c.2080G>T), located in coding exon 18 of the MLH1 gene, results from a G to T substitution at nucleotide position 2080. This changes the amino acid from a glutamic acid to a stop codon within coding exon 18. This alteration was seen in patients with early onset colorectal cancer that showed loss of MLH1 and PMS2 on IHC (Jiang W et al. Int J Cancer, 2019 05;144:2161-2168; Kang SY et al. Int. J. Cancer, 2015 Apr;136:1568-78)). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
CeGaT Center for Human Genetics Tuebingen	RCV001784646	SCV004011456	pathogenic	not provided	2023-04-01	criteria provided, single submitter	clinical testing	MLH1: PVS1, PM2
Myriad Genetics, Inc.	RCV003455442	SCV004186508	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-25	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Ding PR Lab, Sun Yat-sen University Cancer Center	RCV001093683	SCV001250864	likely pathogenic	Lynch syndrome 1		no assertion criteria provided	clinical testing
Laboratory for Genotyping Development, RIKEN	RCV003160614	SCV002758112	pathogenic	Gastric cancer	2021-07-01	no assertion criteria provided	research