Submissions for variant NM_000249.4(MLH1):c.174_175delinsT (p.Leu58fs)

dbSNP: rs876660860

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000215802	SCV000278628	pathogenic	Hereditary cancer-predisposing syndrome	2015-09-16	criteria provided, single submitter	clinical testing	The c.174_175delGAinsT pathogenic mutation, located in coding exon 2 of the MLH1 gene, results from the deletion of two nucleotides and insertion of one nucleotide at positions 174 to 175 causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586133	SCV000696124	likely pathogenic	Lynch syndrome	2017-03-20	criteria provided, single submitter	clinical testing	Variant summary: The MLH1 c.174_175delinsT (p.Leu58Phefs) variant results in a premature termination codon, predicted to cause a truncated or absent MLH1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.178C>T, p.Gln60X; c.298C>T, p.Arg100X; c.184_194del, p.Gln62Hisfs). This variant is absent from 121356 control chromosomes (ExAC dataset). In addition, one clinical diagnostic laboratory classified this variant as pathogenic. Taken together, this variant is classified as Likely Pathogenic.
Myriad Genetics, Inc.	RCV003454660	SCV004186371	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-11	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.