NM_000249.4(MLH1):c.207+5G>C AND Lynch syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 25, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000491027.3

Allele description [Variation Report for NM_000249.4(MLH1):c.207+5G>C]

NM_000249.4(MLH1):c.207+5G>C

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.207+5G>C

HGVS:

NC_000003.12:g.36996714G>C
NG_007109.2:g.8365G>C
NG_008418.1:g.1591C>G
NM_000249.4:c.207+5G>CMANE SELECT
NM_001167617.3:c.-83+5G>C
NM_001167618.3:c.-517+5G>C
NM_001167619.3:c.-425+5G>C
NM_001258271.2:c.207+5G>C
NM_001258273.2:c.-517+3051G>C
NM_001258274.3:c.-662+5G>C
NM_001354615.2:c.-420+5G>C
NM_001354616.2:c.-425+5G>C
NM_001354617.2:c.-517+5G>C
NM_001354618.2:c.-517+5G>C
NM_001354619.2:c.-517+5G>C
NM_001354620.2:c.-83+5G>C
NM_001354621.2:c.-610+5G>C
NM_001354622.2:c.-723+5G>C
NM_001354623.2:c.-723+2824G>C
NM_001354624.2:c.-620+5G>C
NM_001354625.2:c.-523+5G>C
NM_001354626.2:c.-620+5G>C
NM_001354627.2:c.-620+5G>C
NM_001354628.2:c.207+5G>C
NM_001354629.2:c.207+5G>C
NM_001354630.2:c.207+5G>C
LRG_216t1:c.207+5G>C
LRG_216:g.8365G>C
NC_000003.11:g.37038205G>C
NM_000249.3:c.207+5G>C

Links:

dbSNP: rs587781518

NCBI 1000 Genomes Browser:

rs587781518

Molecular consequence:

NM_000249.4:c.207+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001167617.3:c.-83+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001167618.3:c.-517+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001167619.3:c.-425+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001258271.2:c.207+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001258273.2:c.-517+3051G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001258274.3:c.-662+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354615.2:c.-420+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354616.2:c.-425+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354617.2:c.-517+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354618.2:c.-517+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354619.2:c.-517+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354620.2:c.-83+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354621.2:c.-610+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354622.2:c.-723+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2824G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354624.2:c.-620+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354625.2:c.-523+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354626.2:c.-620+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354627.2:c.-620+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354628.2:c.207+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354629.2:c.207+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354630.2:c.207+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Lynch syndrome
Identifiers:: MONDO: MONDO:0005835; MedGen: C4552100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000579490	University of Washington Department of Laboratory Medicine, University of Washington	criteria provided, single submitter (Shirts et al. (Genet Med 2016))	Pathogenic (Mar 25, 2016)	germline, not applicable	clinical testing, in vitro	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000579490

University of Washington Department of Laboratory Medicine, University of Washington

criteria provided, single submitter

(Shirts et al. (Genet Med 2016))

Pathogenic
(Mar 25, 2016)

germline, not applicable

clinical testing, in vitro

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	yes	clinical testing
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro

Citations

PubMed

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC.

Genet Med. 2016 Oct;18(10):974-81. doi: 10.1038/gim.2015.212. Epub 2016 Feb 4.

PubMed [citation]

PMID:: 26845104

Details of each submission

From University of Washington Department of Laboratory Medicine, University of Washington, SCV000579490.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	yes	clinical testing	PubMed (1)
2	not provided	not provided	not provided	not provided	in vitro	PubMed (1)

Description

RNA evidence indicating exon 2 skipping and familial co-segregation analysis indicated evidence for cosegregation of this variant with colon cancers that have loss of MLH1 on IHC (likelihood ratio 25.28, LOD: 1.4). Taken together this is sufficient evidence for variant pathogenicity.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	not applicable	not applicable	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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