Submissions for variant NM_000249.4(MLH1):c.-11C>A

dbSNP: rs776898290

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356927	SCV001552221	uncertain significance	Endometrial carcinoma		no assertion criteria provided	clinical testing	The MLH1 c.-11C>A variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, COGR, Cosmic, UMD-LSDB, Zhejiang University Database, Mismatch Repair Genes Variant Database, Insight Hereditary Tumors databases, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant was identified in our lab with a co-occurring pathogenic MSH6 variant (c.3261dupC, p.Phe1088LeufsX5), increasing the likelihood that the c.-11C>A variant does not have clinical significance. Note another variant, c.-11C>T at the same position with different nucleotide change was found in ClinVar Database and was classified as uncertain significance. In addition, the variant showed a reduction in promoter activity compared to wild type in functional study by Ward (2013). In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.