NM_000249.3(MLH1):c.1219C>T (p.Gln407Ter) AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Pathogenic (Last evaluated: Nov 20, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000684819.2

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:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MedGen: C0009405; Orphanet: 443090

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000543574Invitaecriteria provided, single submitter
Pathogenic
(Nov 20, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000543574.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Gln407*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with sebaceous gland cancer and colorectal cancer (PMID: 26248088), and in individuals affected with Lynch syndrome (PMID: 27601186). ClinVar contains an entry for this variant (Variation ID: 371799). Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 26, 2021

Support Center