NM_000249.4(MLH1):c.1032del (p.Phe344fs) AND Lynch syndrome

Clinical significance:Likely pathogenic (Last evaluated: May 10, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000588814.1

Allele description [Variation Report for NM_000249.4(MLH1):c.1032del (p.Phe344fs)]

NM_000249.4(MLH1):c.1032del (p.Phe344fs)

Gene:
MLH1:mutL homolog 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
3p22.2
Genomic location:
Preferred name:
NM_000249.4(MLH1):c.1032del (p.Phe344fs)
HGVS:
  • NC_000003.12:g.37020457del
  • NG_007109.2:g.32108del
  • NM_000249.4:c.1032delMANE SELECT
  • NM_001167617.3:c.738del
  • NM_001167618.3:c.309del
  • NM_001167619.3:c.309del
  • NM_001258271.2:c.1032del
  • NM_001258273.2:c.309del
  • NM_001258274.3:c.309del
  • NM_001354615.2:c.309del
  • NM_001354616.2:c.309del
  • NM_001354617.2:c.309del
  • NM_001354618.2:c.309del
  • NM_001354619.2:c.309del
  • NM_001354620.2:c.738del
  • NM_001354621.2:c.9del
  • NM_001354622.2:c.9del
  • NM_001354623.2:c.9del
  • NM_001354624.2:c.-36-5180del
  • NM_001354625.2:c.-36-5180del
  • NM_001354626.2:c.-36-5180del
  • NM_001354627.2:c.-36-5180del
  • NM_001354628.2:c.1032del
  • NM_001354629.2:c.933del
  • NM_001354630.2:c.1032del
  • NP_000240.1:p.Phe344fs
  • NP_001161089.1:p.Phe246fs
  • NP_001161090.1:p.Phe103fs
  • NP_001161091.1:p.Phe103fs
  • NP_001245200.1:p.Phe344fs
  • NP_001245202.1:p.Phe103fs
  • NP_001245203.1:p.Phe103fs
  • NP_001341544.1:p.Phe103fs
  • NP_001341545.1:p.Phe103fs
  • NP_001341546.1:p.Phe103fs
  • NP_001341547.1:p.Phe103fs
  • NP_001341548.1:p.Phe103fs
  • NP_001341549.1:p.Phe246fs
  • NP_001341550.1:p.Phe3fs
  • NP_001341551.1:p.Phe3fs
  • NP_001341552.1:p.Phe3fs
  • NP_001341557.1:p.Phe344fs
  • NP_001341558.1:p.Phe311fs
  • NP_001341559.1:p.Phe344fs
  • LRG_216:g.32108del
  • NC_000003.11:g.37061948del
  • NM_000249.3:c.1032delC
  • p.Phe344Leufs*23
Protein change:
F103fs
Links:
dbSNP: rs1553648225
NCBI 1000 Genomes Browser:
rs1553648225
Molecular consequence:
  • NM_000249.4:c.1032del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001167617.3:c.738del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001167618.3:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001167619.3:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001258271.2:c.1032del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001258273.2:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001258274.3:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354615.2:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354616.2:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354617.2:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354618.2:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354619.2:c.309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354620.2:c.738del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354621.2:c.9del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354622.2:c.9del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354623.2:c.9del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354628.2:c.1032del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354629.2:c.933del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354630.2:c.1032del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354624.2:c.-36-5180del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354625.2:c.-36-5180del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354626.2:c.-36-5180del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354627.2:c.-36-5180del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000696091Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(May 10, 2017)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696091.1

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

Description

Variant summary: The MLH1 c.1032delC (p.Phe344Leufs) 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.1210_1211delCT, p.Leu404fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120160 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.

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

Last Updated: Dec 2, 2021

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