Submissions for variant NM_000249.4(MLH1):c.438A>G (p.Gln146=)

gnomAD frequency: 0.00005  dbSNP: rs377279035

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000781994	SCV000920451	likely benign	Lynch syndrome	2018-10-18	reviewed by expert panel	curation	No effect on splicing & Multifactorial Posterior Probabilty = 0.006
Labcorp Genetics (formerly Invitae), Labcorp	RCV000205930	SCV000260540	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000504199	SCV000601400	uncertain significance	not specified	2016-12-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000575797	SCV000669525	likely benign	Hereditary cancer-predisposing syndrome	2015-04-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV000575797	SCV000684830	likely benign	Hereditary cancer-predisposing syndrome	2015-05-29	criteria provided, single submitter	clinical testing
Counsyl	RCV000662701	SCV000785445	uncertain significance	Colorectal cancer, hereditary nonpolyposis, type 2	2017-08-10	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000575797	SCV000821798	likely benign	Hereditary cancer-predisposing syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000662701	SCV001136376	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001594873	SCV001829425	likely benign	not provided	2021-09-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32849802, 31159747, 26096739)
Sema4, Sema4	RCV000575797	SCV002528746	likely benign	Hereditary cancer-predisposing syndrome	2022-03-04	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002494526	SCV002796712	likely benign	Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hereditary nonpolyposis, type 2	2021-10-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000662701	SCV004020242	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2023-03-10	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000504199	SCV004024891	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000781994	SCV004835286	likely benign	Lynch syndrome	2023-12-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001594873	SCV005041842	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	MLH1: BP4, BP7
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353840	SCV000592358	likely benign	Endometrial carcinoma		no assertion criteria provided	clinical testing	The p.Gln146Gln variant has not been previously reported in the literature, public or private databases, nor by our laboratory. This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. In summary, based on the limited amount of information, the clinical significance of this variant could not be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.
Clinical Genetics, Academic Medical Center	RCV001594873	SCV001920323	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001594873	SCV001952252	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003947669	SCV004757297	likely benign	MLH1-related disorder	2021-02-26	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).