U.S. flag

An official website of the United States government

NM_000249.4(MLH1):c.207+1G>C AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 30, 2021
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:
RCV002422121.2

Allele description [Variation Report for NM_000249.4(MLH1):c.207+1G>C]

NM_000249.4(MLH1):c.207+1G>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+1G>C
HGVS:
  • NC_000003.12:g.36996710G>C
  • NG_007109.2:g.8361G>C
  • NG_008418.1:g.1595C>G
  • NM_000249.4:c.207+1G>CMANE SELECT
  • NM_001167617.3:c.-83+1G>C
  • NM_001167618.3:c.-517+1G>C
  • NM_001167619.3:c.-425+1G>C
  • NM_001258271.2:c.207+1G>C
  • NM_001258273.2:c.-517+3047G>C
  • NM_001258274.3:c.-662+1G>C
  • NM_001354615.2:c.-420+1G>C
  • NM_001354616.2:c.-425+1G>C
  • NM_001354617.2:c.-517+1G>C
  • NM_001354618.2:c.-517+1G>C
  • NM_001354619.2:c.-517+1G>C
  • NM_001354620.2:c.-83+1G>C
  • NM_001354621.2:c.-610+1G>C
  • NM_001354622.2:c.-723+1G>C
  • NM_001354623.2:c.-723+2820G>C
  • NM_001354624.2:c.-620+1G>C
  • NM_001354625.2:c.-523+1G>C
  • NM_001354626.2:c.-620+1G>C
  • NM_001354627.2:c.-620+1G>C
  • NM_001354628.2:c.207+1G>C
  • NM_001354629.2:c.207+1G>C
  • NM_001354630.2:c.207+1G>C
  • LRG_216t1:c.207+1G>C
  • LRG_216:g.8361G>C
  • NC_000003.11:g.37038201G>C
  • NM_000249.3:c.207+1G>C
Molecular consequence:
  • NM_001258273.2:c.-517+3047G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354623.2:c.-723+2820G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000249.4:c.207+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001167617.3:c.-83+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001167618.3:c.-517+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001167619.3:c.-425+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258271.2:c.207+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001258274.3:c.-662+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354615.2:c.-420+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354616.2:c.-425+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354617.2:c.-517+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354618.2:c.-517+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354619.2:c.-517+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354620.2:c.-83+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354621.2:c.-610+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354622.2:c.-723+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354624.2:c.-620+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354625.2:c.-523+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354626.2:c.-620+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354627.2:c.-620+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354628.2:c.207+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354629.2:c.207+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001354630.2:c.207+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002727696Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 30, 2021) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV002727696.2

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

Description

The c.207+1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide after coding exon 2 of the MLH1 gene. Another alteration impacting the same donor site (c.207+1G>A) has been shown via RNA studies to result in abnormal splicing in the set of samples tested (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice donor site.Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

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

Last Updated: May 1, 2024