NM_000249.4(MLH1):c.69A>G (p.Glu23=) AND Lynch syndrome

Clinical significance:Likely benign

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001354478.1

Allele description [Variation Report for NM_000249.4(MLH1):c.69A>G (p.Glu23=)]

NM_000249.4(MLH1):c.69A>G (p.Glu23=)

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.69A>G (p.Glu23=)
HGVS:
  • NC_000003.12:g.36993616A>G
  • NG_007109.2:g.5267A>G
  • NG_008418.1:g.4689T>C
  • NM_000249.4:c.69A>GMANE SELECT
  • NM_001167617.3:c.-448A>G
  • NM_001167618.3:c.-877A>G
  • NM_001167619.3:c.-790A>G
  • NM_001258271.2:c.69A>G
  • NM_001258273.2:c.-564A>G
  • NM_001258274.3:c.-1027A>G
  • NM_001354615.2:c.-558A>G
  • NM_001354616.2:c.-558A>G
  • NM_001354617.2:c.-650A>G
  • NM_001354618.2:c.-882A>G
  • NM_001354619.2:c.-1006A>G
  • NM_001354620.2:c.-216A>G
  • NM_001354621.2:c.-975A>G
  • NM_001354622.2:c.-1088A>G
  • NM_001354623.2:c.-997A>G
  • NM_001354624.2:c.-758A>G
  • NM_001354625.2:c.-656A>G
  • NM_001354626.2:c.-753A>G
  • NM_001354627.2:c.-985A>G
  • NM_001354628.2:c.69A>G
  • NM_001354629.2:c.69A>G
  • NM_001354630.2:c.69A>G
  • NP_000240.1:p.Glu23=
  • NP_000240.1:p.Glu23=
  • NP_001245200.1:p.Glu23=
  • NP_001341557.1:p.Glu23=
  • NP_001341558.1:p.Glu23=
  • NP_001341559.1:p.Glu23=
  • LRG_216t1:c.69A>G
  • LRG_216:g.5267A>G
  • LRG_216p1:p.Glu23=
  • NC_000003.11:g.37035107A>G
  • NM_000249.3:c.69A>G
  • p.E23E
  • p.Glu23Glu
Links:
dbSNP: rs63750555
NCBI 1000 Genomes Browser:
rs63750555
Molecular consequence:
  • NM_001167617.3:c.-448A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001167618.3:c.-877A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001167619.3:c.-790A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258273.2:c.-564A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258274.3:c.-1027A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354615.2:c.-558A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354616.2:c.-558A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354617.2:c.-650A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354618.2:c.-882A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354619.2:c.-1006A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354620.2:c.-216A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354621.2:c.-975A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354622.2:c.-1088A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354623.2:c.-997A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354624.2:c.-758A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354625.2:c.-656A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354626.2:c.-753A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354627.2:c.-985A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000249.4:c.69A>G - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001258271.2:c.69A>G - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354628.2:c.69A>G - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354629.2:c.69A>G - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354630.2:c.69A>G - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV001549105Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedLikely benignunknownclinical testing

Summary from all submissions

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

Details of each submission

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001549105.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The MLH1 p.Glu23= variant was not identified in the literature nor was it identified in the UMD-LSDB. The variant was identified in dbSNP (ID: rs63750555) as "With Uncertain significance allele" and in ClinVar (classified as likely benign by Invitae, Ambry Genetics, Color and Counsyl; as uncertain significance by one submitter). The variant was identified in control databases in 2 of 246094 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in European population in 2 of 111564 chromosomes (freq: 0.00002), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Glu23= 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,) 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.

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

Last Updated: Dec 4, 2021

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