Submissions for variant NM_000249.4(MLH1):c.1831_1832del (p.Ile611fs)

dbSNP: rs63750150

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000075376	SCV000106371	pathogenic	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Coding sequence variation resulting in a stop codon
Invitae	RCV001381499	SCV001579923	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2020-07-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile611Cysfs*2) 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 Lynch syndrome (PMID: 15253764). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 89899). 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.	RCV003451070	SCV004186307	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-24	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353580	SCV000592422	uncertain significance	not provided		no assertion criteria provided	clinical testing
GeneReviews	RCV001804817	SCV002054057	not provided	Lynch syndrome 1		no assertion provided	literature only