GI tract tumours

Gene: MLH1

As discussed in the GMS Inherited Cancer Specialist Test Group webex call 31st Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.

Created: 31 Jul 2019, 12:26 p.m. | Last Modified: 31 Jul 2019, 12:26 p.m.

Panel Version: 1.13

Green List (high evidence)

Publications

• 29661970

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Comment when marking as ready: Associated with phenotypes in OMIM and as a confirmed G2P associateions. At least 8 variants reported in Mismatch repair cancer syndrome 276300 and one in Muir-Torre syndrome 158320, however, these phenotypes do not include hamartomatous polyps characteristic of Peutz-Jeghers syndrome. No polyps are associated with colorectal cancer, hereditary nonpolyposis, type 2 609310

Created: 11 Apr 2017, 3:01 p.m.

Comment on phenotypes: Also associated with Colorectal cancer, hereditary nonpolyposis, type 2 609310

Created: 11 Apr 2017, 2:57 p.m.

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Comment on list classification: Current diagnostic.

Created: 7 Feb 2016, 9:16 p.m.

Green List (high evidence)

http://chromium.lovd.nl/LOVD2/colon_cancer/home.php?select_db=MLH1
Biallelic mutations cause Constitutional Mismatch Repair Disorder (CMMR-D)

Created: 8 Dec 2015, 2:21 p.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Publications

• Thompson BA, Spurdle AB, Plazzer J-P, Greenblatt M, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capella G, du Sart D, Fabre A, Farrell MP, Farrington S, Frayling IM, et al., on behalf of InSiGHT, Macrae F, Genuardi M. (2014) Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nature Genetics 46:107-115
• doi:10.1038/ng.2854.