ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.30G>T (p.Arg10=) (rs876660759)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001354490 SCV000518369 likely benign not provided 2020-02-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000566157 SCV000662042 likely benign Hereditary cancer-predisposing syndrome 2016-03-31 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Color Health, Inc RCV000566157 SCV000689877 likely benign Hereditary cancer-predisposing syndrome 2017-09-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000443088 SCV000696157 likely benign not specified 2019-08-29 criteria provided, single submitter clinical testing
Invitae RCV000630358 SCV000751314 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-06 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354490 SCV001549119 uncertain significance not provided no assertion criteria provided clinical testing The MLH1 p.Arg10= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, UMD-LSDB, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, or the Insight Hereditary Tumors database. The variant was identified in dbSNP (ID: rs876660759) as "With Likely benign allele", ClinVar (classified as likely benign by GeneDx, Ambry Genetics, Color Genomics, Invitae; as uncertain significance by Integrated Genetics/Laboratory Corporation of America), and Clinvitae databases. The variant was identified in control databases in 2 of 277228 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 1 of 24038 chromosomes (freq: 0.00004), European in 1 of 126712 chromosomes (freq: 0.00002), while the variant was not observed in the Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Arg10= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. 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.

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