ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.-28A>T

dbSNP: rs56198082
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480574 SCV000566000 uncertain significance not provided 2020-01-16 criteria provided, single submitter clinical testing Describes a nucleotide substitution 28 base pairs upstream of the ATG translational start site in the 5' untranslated region (5'UTR) of the MLH1 gene; Observed in individuals with suspected Lynch syndrome (Isidro 2003, Mangold 2005); Has no predicted effect on splicing and the nucleotide is not conserved across species; Also known as c.1-28A>T; This variant is associated with the following publications: (PMID: 23315997, 14517962, 25762362, 15849733)
Color Diagnostics, LLC DBA Color Health RCV001191287 SCV001359044 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-06 criteria provided, single submitter clinical testing This variant is located in the 5' untranslated region of the MLH1 gene. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with colorectal cancer and suspected Lynch syndrome (PMID: 14517962, 15849733). This variant has been identified in 2/251454 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854288 SCV002144829 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-06-27 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of this non-coding change is currently unknown. This variant has been observed in several individuals affected with colorectal cancer (PMID: 14517962, 15849733). ClinVar contains an entry for this variant (Variation ID: 89591). This variant is present in population databases (rs56198082, ExAC 0.009%). This variant occurs in a non-coding region of the MLH1 gene. It does not change the encoded amino acid sequence of the MLH1 protein.
Baylor Genetics RCV004566927 SCV005057957 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 2 2024-03-19 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004566927 SCV005896252 benign Colorectal cancer, hereditary nonpolyposis, type 2 2024-11-19 criteria provided, single submitter clinical testing This variant is considered benign. This variant occurs in the non-coding 5' untranslated region of the gene, and is not expected to impact protein function.

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