NM_000249.4(MLH1):c.583A>T (p.Lys195Ter) AND not provided

Clinical significance:Pathogenic (Last evaluated: Oct 31, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000202144.1

Allele description [Variation Report for NM_000249.4(MLH1):c.583A>T (p.Lys195Ter)]

NM_000249.4(MLH1):c.583A>T (p.Lys195Ter)

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.583A>T (p.Lys195Ter)
HGVS:
  • NC_000003.12:g.37011857A>T
  • NG_007109.2:g.23508A>T
  • NM_000249.3:c.583A>T
  • NM_000249.4:c.583A>TMANE SELECT
  • NM_001167617.3:c.289A>T
  • NM_001167618.3:c.-141A>T
  • NM_001167619.3:c.-141A>T
  • NM_001258271.2:c.583A>T
  • NM_001258273.2:c.-141A>T
  • NM_001258274.3:c.-141A>T
  • NM_001354615.2:c.-141A>T
  • NM_001354616.2:c.-141A>T
  • NM_001354617.2:c.-141A>T
  • NM_001354618.2:c.-141A>T
  • NM_001354619.2:c.-141A>T
  • NM_001354620.2:c.289A>T
  • NM_001354621.2:c.-234A>T
  • NM_001354622.2:c.-347A>T
  • NM_001354623.2:c.-347A>T
  • NM_001354624.2:c.-244A>T
  • NM_001354625.2:c.-244A>T
  • NM_001354626.2:c.-244A>T
  • NM_001354627.2:c.-244A>T
  • NM_001354628.2:c.583A>T
  • NM_001354629.2:c.484A>T
  • NM_001354630.2:c.583A>T
  • NP_000240.1:p.Lys195Ter
  • NP_000240.1:p.Lys195Ter
  • NP_001161089.1:p.Lys97Ter
  • NP_001245200.1:p.Lys195Ter
  • NP_001341549.1:p.Lys97Ter
  • NP_001341557.1:p.Lys195Ter
  • NP_001341558.1:p.Lys162Ter
  • NP_001341559.1:p.Lys195Ter
  • LRG_216t1:c.583A>T
  • LRG_216:g.23508A>T
  • LRG_216p1:p.Lys195Ter
  • NC_000003.11:g.37053348A>T
Protein change:
K162*
Links:
dbSNP: rs863225383
NCBI 1000 Genomes Browser:
rs863225383
Molecular consequence:
  • NM_001167618.3:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001167619.3:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258273.2:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258274.3:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354615.2:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354616.2:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354617.2:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354618.2:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354619.2:c.-141A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354621.2:c.-234A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354622.2:c.-347A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354623.2:c.-347A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354624.2:c.-244A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354625.2:c.-244A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354626.2:c.-244A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354627.2:c.-244A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000249.3:c.583A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000249.4:c.583A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001167617.3:c.289A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001258271.2:c.583A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354620.2:c.289A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354628.2:c.583A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354629.2:c.484A>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354630.2:c.583A>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000257105Mayo Clinic Laboratories, Mayo Clinicno assertion criteria providedLikely pathogenicunknownresearch

SCV000779388GeneDxcriteria provided, single submitter
Pathogenic
(Oct 31, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknown1not providednot providednot providednot providedresearch

Details of each submission

From Mayo Clinic Laboratories, Mayo Clinic, SCV000257105.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000779388.1

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

Description

This variant is denoted MLH1 c.583A>T at the cDNA level and p.Lys195Ter (K195X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with Lynch syndrome (Hinrichsen 2015, Binder 2017) and is considered pathogenic.

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

Last Updated: Oct 25, 2021

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