Submissions for variant NM_000249.4(MLH1):c.866_867dup (p.Pro290fs)

dbSNP: rs587779047

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000075895	SCV000106911	pathogenic	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Coding sequence variation resulting in a stop codon
Invitae	RCV001388083	SCV001588930	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2020-08-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro290Thrfs*8) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 19995443). ClinVar contains an entry for this variant (Variation ID: 90402). Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV003452779	SCV004186417	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-18	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.