NM_000249.4(MLH1):c.673dup (p.Ser225fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 19, 2019
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:: RCV001025597.3

Allele description [Variation Report for NM_000249.4(MLH1):c.673dup (p.Ser225fs)]

NM_000249.4(MLH1):c.673dup (p.Ser225fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.673dup (p.Ser225fs)

HGVS:

NC_000003.12:g.37012095dup
NG_007109.2:g.23746dup
NM_000249.4:c.673dupMANE SELECT
NM_001167617.3:c.379dup
NM_001167618.3:c.-51dup
NM_001167619.3:c.-51dup
NM_001258271.2:c.673dup
NM_001258273.2:c.-51dup
NM_001258274.3:c.-51dup
NM_001354615.2:c.-51dup
NM_001354616.2:c.-51dup
NM_001354617.2:c.-51dup
NM_001354618.2:c.-51dup
NM_001354619.2:c.-51dup
NM_001354620.2:c.379dup
NM_001354621.2:c.-144dup
NM_001354622.2:c.-257dup
NM_001354623.2:c.-257dup
NM_001354624.2:c.-154dup
NM_001354625.2:c.-154dup
NM_001354626.2:c.-154dup
NM_001354627.2:c.-154dup
NM_001354628.2:c.673dup
NM_001354629.2:c.574dup
NM_001354630.2:c.673dup
NP_000240.1:p.Ser225fs
NP_001161089.1:p.Ser127fs
NP_001245200.1:p.Ser225fs
NP_001341549.1:p.Ser127fs
NP_001341557.1:p.Ser225fs
NP_001341558.1:p.Ser192fs
NP_001341559.1:p.Ser225fs
LRG_216t1:c.673dup
LRG_216:g.23746dup
NC_000003.11:g.37053585_37053586insA
NC_000003.11:g.37053586dup
NM_000249.3:c.673dupA
p.Ser225Lysfs*10

Protein change:

S127fs

Links:

dbSNP: rs1575469505

NCBI 1000 Genomes Browser:

rs1575469505

Molecular consequence:

NM_001167618.3:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-51dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-144dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-257dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-257dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-154dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-154dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-154dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-154dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.673dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167617.3:c.379dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.673dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354620.2:c.379dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.673dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.574dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.673dup - 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

Recent activity

Clear Turn Off Turn On

Homo sapiens zinc finger and BTB domain containing 7B (ZBTB7B), mRNA
Homo sapiens zinc finger and BTB domain containing 7B (ZBTB7B), mRNA
gi|7705663|ref|NM_015872.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001187818	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 19, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001187818

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 19, 2019)

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, SCV001187818.4

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

Description

The c.673dupA pathogenic mutation, located in coding exon 8 of the MLH1 gene, results from a duplication of A at nucleotide position 673, causing a translational frameshift with a predicted alternate stop codon (p.S225Kfs*10). This mutation has been reported in one British HNPCC family (Taylor CF et al. Hum Mutat. 2003 Dec;22(6):428-33). 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. This nucleotide position is highly conserved in available vertebrate species.

#	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

ClinVar

Relating variation to medicine