NM_000249.4(MLH1):c.651delinsTTA (p.Ser218fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 7, 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:: RCV002364220.2

Allele description [Variation Report for NM_000249.4(MLH1):c.651delinsTTA (p.Ser218fs)]

NM_000249.4(MLH1):c.651delinsTTA (p.Ser218fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.651delinsTTA (p.Ser218fs)

HGVS:

NC_000003.12:g.37012073delinsTTA
NG_007109.2:g.23724delinsTTA
NM_000249.4:c.651delinsTTAMANE SELECT
NM_001167617.3:c.357delinsTTA
NM_001167618.3:c.-73delinsTTA
NM_001167619.3:c.-73delinsTTA
NM_001258271.2:c.651delinsTTA
NM_001258273.2:c.-73delinsTTA
NM_001258274.3:c.-73delinsTTA
NM_001354615.2:c.-73delinsTTA
NM_001354616.2:c.-73delinsTTA
NM_001354617.2:c.-73delinsTTA
NM_001354618.2:c.-73delinsTTA
NM_001354619.2:c.-73delinsTTA
NM_001354620.2:c.357delinsTTA
NM_001354621.2:c.-166delinsTTA
NM_001354622.2:c.-279delinsTTA
NM_001354623.2:c.-279delinsTTA
NM_001354624.2:c.-176delinsTTA
NM_001354625.2:c.-176delinsTTA
NM_001354626.2:c.-176delinsTTA
NM_001354627.2:c.-176delinsTTA
NM_001354628.2:c.651delinsTTA
NM_001354629.2:c.552delinsTTA
NM_001354630.2:c.651delinsTTA
NP_000240.1:p.Ser218Tyrfs
NP_000240.1:p.Ser218fs
NP_001161089.1:p.Ser120fs
NP_001245200.1:p.Ser218fs
NP_001341549.1:p.Ser120fs
NP_001341557.1:p.Ser218fs
NP_001341558.1:p.Ser185fs
NP_001341559.1:p.Ser218fs
LRG_216t1:c.651delCinsTTA
LRG_216:g.23724delinsTTA
LRG_216p1:p.Ser218Tyrfs
NC_000003.11:g.37053564delinsTTA
NM_000249.3:c.651delCinsTTA

Protein change:

S120fs

Molecular consequence:

NM_001167618.3:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-73delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-166delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-279delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-279delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-176delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-176delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-176delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-176delinsTTA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.651delinsTTA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167617.3:c.357delinsTTA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.651delinsTTA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354620.2:c.357delinsTTA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.651delinsTTA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.552delinsTTA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.651delinsTTA - 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
SCV002660145	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 7, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002660145

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 7, 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, SCV002660145.2

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

Description

The c.651delCinsTTA pathogenic mutation, located in coding exon 8 of the MLH1 gene, results from the deletion of one nucleotide and insertion of 3 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.S218Yfs*12). 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: May 1, 2024

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