NM_000249.4(MLH1):c.71_75del (p.Val24fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 8, 2024
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:: RCV002367731.2

Allele description [Variation Report for NM_000249.4(MLH1):c.71_75del (p.Val24fs)]

NM_000249.4(MLH1):c.71_75del (p.Val24fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.71_75del (p.Val24fs)

HGVS:

NC_000003.12:g.36993618_36993622del
NG_007109.2:g.5269_5273del
NG_008418.1:g.4683_4687del
NM_000249.4:c.71_75delMANE SELECT
NM_001167617.3:c.-446_-442del
NM_001167618.3:c.-875_-871del
NM_001167619.3:c.-788_-784del
NM_001258271.2:c.71_75del
NM_001258273.2:c.-562_-558del
NM_001258274.3:c.-1025_-1021del
NM_001354615.2:c.-556_-552del
NM_001354616.2:c.-556_-552del
NM_001354617.2:c.-648_-644del
NM_001354618.2:c.-880_-876del
NM_001354619.2:c.-1004_-1000del
NM_001354620.2:c.-214_-210del
NM_001354621.2:c.-973_-969del
NM_001354622.2:c.-1086_-1082del
NM_001354623.2:c.-995_-991del
NM_001354624.2:c.-756_-752del
NM_001354625.2:c.-654_-650del
NM_001354626.2:c.-751_-747del
NM_001354627.2:c.-983_-979del
NM_001354628.2:c.71_75del
NM_001354629.2:c.71_75del
NM_001354630.2:c.71_75del
NP_000240.1:p.Val24fs
NP_001245200.1:p.Val24fs
NP_001341557.1:p.Val24fs
NP_001341558.1:p.Val24fs
NP_001341559.1:p.Val24fs
LRG_216:g.5269_5273del
NC_000003.11:g.37035109_37035113del
NM_000249.3:c.71_75delTTATC

Protein change:

V24fs

Links:

dbSNP: rs1553637293

NCBI 1000 Genomes Browser:

rs1553637293

Molecular consequence:

NM_001167617.3:c.-446_-442del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-875_-871del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-788_-784del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-562_-558del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-1025_-1021del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-556_-552del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-556_-552del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-648_-644del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-880_-876del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-1004_-1000del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-214_-210del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-973_-969del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-1086_-1082del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-995_-991del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-756_-752del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-654_-650del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-751_-747del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-983_-979del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.71_75del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.71_75del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.71_75del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.71_75del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.71_75del - 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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PLA2G2A [Rhinolophus ferrumequinum]
Gene ID:117026523

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002662620	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 8, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002662620

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 8, 2024)

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, SCV002662620.2

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

Description

The c.71_75delTTATC pathogenic mutation, located in coding exon 1 of the MLH1 gene, results from a deletion of 5 nucleotides at nucleotide positions 71 to 75, causing a translational frameshift with a predicted alternate stop codon (p.V24Afs*5). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 7, 2024

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