NM_000249.4(MLH1):c.201dup (p.Ile68fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 12, 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:: RCV002418500.2

Allele description [Variation Report for NM_000249.4(MLH1):c.201dup (p.Ile68fs)]

NM_000249.4(MLH1):c.201dup (p.Ile68fs)

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.201dup (p.Ile68fs)

HGVS:

NC_000003.12:g.36996703dup
NG_007109.2:g.8354dup
NG_008418.1:g.1604dup
NM_000249.4:c.201dupMANE SELECT
NM_001167617.3:c.-89dup
NM_001167618.3:c.-523dup
NM_001167619.3:c.-431dup
NM_001258271.2:c.201dup
NM_001258273.2:c.-517+3040dup
NM_001258274.3:c.-668dup
NM_001354615.2:c.-426dup
NM_001354616.2:c.-431dup
NM_001354617.2:c.-523dup
NM_001354618.2:c.-523dup
NM_001354619.2:c.-523dup
NM_001354620.2:c.-89dup
NM_001354621.2:c.-616dup
NM_001354622.2:c.-729dup
NM_001354623.2:c.-723+2813dup
NM_001354624.2:c.-626dup
NM_001354625.2:c.-529dup
NM_001354626.2:c.-626dup
NM_001354627.2:c.-626dup
NM_001354628.2:c.201dup
NM_001354629.2:c.201dup
NM_001354630.2:c.201dup
NP_000240.1:p.Ile68fs
NP_000240.1:p.Ile68fs
NP_001245200.1:p.Ile68fs
NP_001341557.1:p.Ile68fs
NP_001341558.1:p.Ile68fs
NP_001341559.1:p.Ile68fs
LRG_216t1:c.201dup
LRG_216:g.8354dup
LRG_216p1:p.Ile68fs
NC_000003.11:g.37038191_37038192insG
NC_000003.11:g.37038194dup
NM_000249.3:c.201dup
NM_000249.3:c.201dupG

Protein change:

I68fs

Links:

dbSNP: rs587778968

NCBI 1000 Genomes Browser:

rs587778968

Molecular consequence:

NM_001167617.3:c.-89dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-523dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-431dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-668dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-426dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-431dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-523dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-523dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-523dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-89dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-616dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-729dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-626dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-529dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-626dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-626dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.201dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.201dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.201dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.201dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.201dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258273.2:c.-517+3040dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2813dup - intron variant - [Sequence Ontology: SO:0001627]

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

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PubChem Substance Links for Gene (Select 285971) (72)
PubChem Substance
LINC02868 long intergenic non-protein coding RNA 2868 [Homo sapiens]
LINC02868 long intergenic non-protein coding RNA 2868 [Homo sapiens]
Gene ID:388667

Gene
homo sapiens[Organism] AND C1orf137 AND (alive[prop]) (1)
Gene
Inga paraensis (1)
Taxonomy
geranyl diphosphate phosphohydrolase [Momordica charantia]
geranyl diphosphate phosphohydrolase [Momordica charantia]
gi|1229791209|ref|XP_022149108.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002723749	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 12, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002723749

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 12, 2021)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV002723749.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.201dupG pathogenic mutation, located in coding exon 2 of the MLH1 gene, results from a duplication of G at nucleotide position 201, causing a translational frameshift with a predicted alternate stop codon (p.I68Dfs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024

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