NM_000249.3(MLH1):c.1219C>T (p.Gln407Ter) AND Lynch syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 5, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000464749.5

Allele description [Variation Report for NM_000249.3(MLH1):c.1219C>T (p.Gln407Ter)]

NM_000249.3(MLH1):c.1219C>T (p.Gln407Ter)

Gene:
MLH1:mutL homolog 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p22.2
Genomic location:
Preferred name:
NM_000249.3(MLH1):c.1219C>T (p.Gln407Ter)
HGVS:
  • NC_000003.12:g.37025817C>T
  • NG_007109.2:g.37468C>T
  • NM_000249.3:c.1219C>T
  • NM_001167617.2:c.925C>T
  • NM_001167618.2:c.496C>T
  • NM_001167619.2:c.496C>T
  • NM_001258271.1:c.1219C>T
  • NM_001258273.1:c.496C>T
  • NM_001258274.2:c.496C>T
  • NM_001354615.1:c.496C>T
  • NM_001354616.1:c.496C>T
  • NM_001354617.1:c.496C>T
  • NM_001354618.1:c.496C>T
  • NM_001354619.1:c.496C>T
  • NM_001354620.1:c.925C>T
  • NM_001354621.1:c.196C>T
  • NM_001354622.1:c.196C>T
  • NM_001354623.1:c.196C>T
  • NM_001354624.1:c.145C>T
  • NM_001354625.1:c.145C>T
  • NM_001354626.1:c.145C>T
  • NM_001354627.1:c.145C>T
  • NM_001354628.1:c.1219C>T
  • NM_001354629.1:c.1120C>T
  • NM_001354630.1:c.1219C>T
  • NP_000240.1:p.Gln407Ter
  • NP_001161089.1:p.Gln309Ter
  • NP_001161090.1:p.Gln166Ter
  • NP_001161091.1:p.Gln166Ter
  • NP_001245200.1:p.Gln407Ter
  • NP_001245202.1:p.Gln166Ter
  • NP_001245203.1:p.Gln166Ter
  • NP_001341544.1:p.Gln166Ter
  • NP_001341545.1:p.Gln166Ter
  • NP_001341546.1:p.Gln166Ter
  • NP_001341547.1:p.Gln166Ter
  • NP_001341548.1:p.Gln166Ter
  • NP_001341549.1:p.Gln309Ter
  • NP_001341550.1:p.Gln66Ter
  • NP_001341551.1:p.Gln66Ter
  • NP_001341552.1:p.Gln66Ter
  • NP_001341553.1:p.Gln49Ter
  • NP_001341554.1:p.Gln49Ter
  • NP_001341555.1:p.Gln49Ter
  • NP_001341556.1:p.Gln49Ter
  • NP_001341557.1:p.Gln407Ter
  • NP_001341558.1:p.Gln374Ter
  • NP_001341559.1:p.Gln407Ter
  • LRG_216t1:c.1219C>T
  • LRG_216:g.37468C>T
  • LRG_216p1:p.Gln407Ter
  • NC_000003.11:g.37067308C>T
  • p.Gln407*
Protein change:
Q166*
Links:
dbSNP: rs1057517541
NCBI 1000 Genomes Browser:
rs1057517541
Molecular consequence:
  • NM_000249.3:c.1219C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001167617.2:c.925C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001167618.2:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001167619.2:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001258271.1:c.1219C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001258273.1:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001258274.2:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354615.1:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354616.1:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354617.1:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354618.1:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354619.1:c.496C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354620.1:c.925C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354621.1:c.196C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354622.1:c.196C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354623.1:c.196C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354624.1:c.145C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354625.1:c.145C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354626.1:c.145C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354627.1:c.145C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354628.1:c.1219C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354629.1:c.1120C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354630.1:c.1219C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000919637Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Sep 5, 2017)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population.

Lagerstedt-Robinson K, Rohlin A, Aravidis C, Melin B, Nordling M, Stenmark-Askmalm M, Lindblom A, Nilbert M.

Oncol Rep. 2016 Nov;36(5):2823-2835. doi: 10.3892/or.2016.5060. Epub 2016 Sep 1.

PubMed [citation]
PMID:
27601186

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919637.1

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

Description

Variant summary: The MLH1 c.1219C>T (p.Gln407X) variant results in a premature termination codon, predicted to cause a truncated or absent MLH1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1381A>T, p.Lys461X; c.1459C>T, p.Arg487X; c.1489dupC, p.Arg497fsX6). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121406 control chromosomes. The variant was reported in individuals and families affected by Lynch syndrome (Guindalini 2015, Lagerstedt-Robinson 2016). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Sep 26, 2021

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