NM_000249.4(MLH1):c.678-1G>A AND Lynch syndrome

Clinical significance:Likely pathogenic (Last evaluated: May 1, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000758642.1

Allele description [Variation Report for NM_000249.4(MLH1):c.678-1G>A]

NM_000249.4(MLH1):c.678-1G>A

Gene:
MLH1:mutL homolog 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p22.2
Genomic location:
Preferred name:
NM_000249.4(MLH1):c.678-1G>A
HGVS:
  • NC_000003.12:g.37014431G>A
  • NG_007109.2:g.26082G>A
  • NM_000249.4:c.678-1G>AMANE SELECT
  • NM_001167617.3:c.384-1G>A
  • NM_001167618.3:c.-46-1G>A
  • NM_001167619.3:c.-46-1G>A
  • NM_001258271.2:c.678-1G>A
  • NM_001258273.2:c.-46-1G>A
  • NM_001258274.3:c.-46-1G>A
  • NM_001354615.2:c.-46-1G>A
  • NM_001354616.2:c.-46-1G>A
  • NM_001354617.2:c.-46-1G>A
  • NM_001354618.2:c.-46-1G>A
  • NM_001354619.2:c.-46-1G>A
  • NM_001354620.2:c.384-1G>A
  • NM_001354621.2:c.-140+2332G>A
  • NM_001354622.2:c.-252-1G>A
  • NM_001354623.2:c.-252-1G>A
  • NM_001354624.2:c.-149-1G>A
  • NM_001354625.2:c.-149-1G>A
  • NM_001354626.2:c.-149-1G>A
  • NM_001354627.2:c.-149-1G>A
  • NM_001354628.2:c.678-1G>A
  • NM_001354629.2:c.579-1G>A
  • NM_001354630.2:c.678-1G>A
  • LRG_216t1:c.678-1G>A
  • LRG_216:g.26082G>A
  • NC_000003.11:g.37055922G>A
  • NM_000249.3:c.678-1G>A
Links:
dbSNP: rs267607784
NCBI 1000 Genomes Browser:
rs267607784
Molecular consequence:
  • NM_001354621.2:c.-140+2332G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000249.4:c.678-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001167617.3:c.384-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001167618.3:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001167619.3:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001258271.2:c.678-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001258273.2:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001258274.3:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354615.2:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354616.2:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354617.2:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354618.2:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354619.2:c.-46-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354620.2:c.384-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354622.2:c.-252-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354623.2:c.-252-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354624.2:c.-149-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354625.2:c.-149-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354626.2:c.-149-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354627.2:c.-149-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354628.2:c.678-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354629.2:c.579-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001354630.2:c.678-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Lynch syndrome
Synonyms:
Familial nonpolyposis colon cancer
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100; OMIM: PS120435

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000887401University of Washington Department of Laboratory Medicine, University of Washingtoncriteria provided, single submitter
Likely pathogenic
(May 1, 2018)
somaticclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Using Somatic Mutations from Tumors to Classify Variants in Mismatch Repair Genes.

Shirts BH, Konnick EQ, Upham S, Walsh T, Ranola JMO, Jacobson AL, King MC, Pearlman R, Hampel H, Pritchard CC.

Am J Hum Genet. 2018 Jul 5;103(1):19-29. doi: 10.1016/j.ajhg.2018.05.001. Epub 2018 Jun 7.

PubMed [citation]
PMID:
29887214
PMCID:
PMC6035155

Details of each submission

From University of Washington Department of Laboratory Medicine, University of Washington, SCV000887401.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

MLH1 NM_000249.3:c.678-1G>A has a 98.1% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 1.56 to 1, generated from evidence of seeing this as a somatic mutation in a tumor without loss of heterozygosity at the MLH1 locus. See Shirts et al 2018, PMID 29887214.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1somaticyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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