ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3162C>T (p.Ile1054=) (rs149605979)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163126 SCV000213638 likely benign Hereditary cancer-predisposing syndrome 2015-09-23 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001087949 SCV000260097 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000423495 SCV000513696 benign not specified 2015-04-23 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000423495 SCV000601560 likely benign not specified 2016-09-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163126 SCV000690318 likely benign Hereditary cancer-predisposing syndrome 2017-07-27 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679232 SCV000805877 likely benign not provided 2017-08-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679232 SCV000889485 benign not provided 2017-08-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000423495 SCV001363906 likely benign not specified 2019-12-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285803 SCV001472289 likely benign none provided 2019-10-13 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357025 SCV001552349 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH6 p.Ile1054= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, MutDB, UMD-LSDB, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs149605979) as “With Likely benign allele” , ClinVar (as benign by Gene Dx and likely benign by Ambry Genetics, Invitae, and Quest Diagnostics), Clinvitae (3x as benign and likely benign), and Cosmic (1x in bile duct carcinoma) databases. The variant was identified in control databases in 26 of 272178 chromosomes at a frequency of 0.000096 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 20 of 23926 chromosomes (freq: 0.000836), Latino in 1 of 34350 chromosomes (freq: 0.000029), European (Non-Finnish) in 1 of 125540 chromosomes (freq: 0.000008), East Asian in 2 of 18794 chromosomes (freq: 0.000106), European (Finnish) in 2 of 22290 chromosomes (freq: 0.00009), while the variant was not observed in the Other, Ashkenaz iJewish, and South Asian populations. The p.Ile1054= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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