NM_000249.4(MLH1):c.2187_2190dup (p.Pro731fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 19, 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:: RCV002425493.2

Allele description [Variation Report for NM_000249.4(MLH1):c.2187_2190dup (p.Pro731fs)]

NM_000249.4(MLH1):c.2187_2190dup (p.Pro731fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.2187_2190dup (p.Pro731fs)

HGVS:

NC_000003.12:g.37050569_37050572dup
NG_007109.2:g.62220_62223dup
NM_000249.4:c.2187_2190dupMANE SELECT
NM_001167617.3:c.1893_1896dup
NM_001167618.3:c.1464_1467dup
NM_001167619.3:c.1464_1467dup
NM_001258271.2:c.1980_1983dup
NM_001258273.2:c.1464_1467dup
NM_001258274.3:c.1464_1467dup
NM_001354615.2:c.1464_1467dup
NM_001354616.2:c.1464_1467dup
NM_001354617.2:c.1464_1467dup
NM_001354618.2:c.1464_1467dup
NM_001354619.2:c.1464_1467dup
NM_001354620.2:c.1893_1896dup
NM_001354621.2:c.1164_1167dup
NM_001354622.2:c.1164_1167dup
NM_001354623.2:c.1164_1167dup
NM_001354624.2:c.1113_1116dup
NM_001354625.2:c.1113_1116dup
NM_001354626.2:c.1113_1116dup
NM_001354627.2:c.1113_1116dup
NM_001354628.2:c.2094_2097dup
NM_001354629.2:c.2088_2091dup
NM_001354630.2:c.2022_2025dup
NP_000240.1:p.Pro731Alafs
NP_000240.1:p.Pro731fs
NP_001161089.1:p.Pro633fs
NP_001161090.1:p.Pro490fs
NP_001161091.1:p.Pro490fs
NP_001245200.1:p.Pro662fs
NP_001245202.1:p.Pro490fs
NP_001245203.1:p.Pro490fs
NP_001341544.1:p.Pro490fs
NP_001341545.1:p.Pro490fs
NP_001341546.1:p.Pro490fs
NP_001341547.1:p.Pro490fs
NP_001341548.1:p.Pro490fs
NP_001341549.1:p.Pro633fs
NP_001341550.1:p.Pro390fs
NP_001341551.1:p.Pro390fs
NP_001341552.1:p.Pro390fs
NP_001341553.1:p.Pro373fs
NP_001341554.1:p.Pro373fs
NP_001341555.1:p.Pro373fs
NP_001341556.1:p.Pro373fs
NP_001341557.1:p.Pro700fs
NP_001341558.1:p.Pro698fs
NP_001341559.1:p.Pro676fs
LRG_216t1:c.2187_2190dup
LRG_216:g.62220_62223dup
LRG_216p1:p.Pro731Alafs
NC_000003.11:g.37092060_37092063dup
NM_000249.3:c.2187_2190dup
NM_000249.3:c.2187_2190dupGCCT

Protein change:

P373fs

Molecular consequence:

NM_000249.4:c.2187_2190dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167617.3:c.1893_1896dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167618.3:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167619.3:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.1980_1983dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258273.2:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258274.3:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354615.2:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354616.2:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354617.2:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354618.2:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354619.2:c.1464_1467dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354620.2:c.1893_1896dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354621.2:c.1164_1167dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354622.2:c.1164_1167dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354623.2:c.1164_1167dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354624.2:c.1113_1116dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354625.2:c.1113_1116dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354626.2:c.1113_1116dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354627.2:c.1113_1116dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.2094_2097dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.2088_2091dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.2022_2025dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002730154	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 19, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002730154

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 19, 2016)

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, SCV002730154.2

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

Description

The c.2187_2190dupGCCT pathogenic mutation, located in coding exon 19 of the MLH1 gene, results from a duplication of GCCT at nucleotide position 2187, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

#	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: May 1, 2024

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