NM_000249.4(MLH1):c.175A>G (p.Ile59Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 16, 2023
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:: RCV003365612.2

Allele description [Variation Report for NM_000249.4(MLH1):c.175A>G (p.Ile59Val)]

NM_000249.4(MLH1):c.175A>G (p.Ile59Val)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.175A>G (p.Ile59Val)

HGVS:

NC_000003.12:g.36996677A>G
NG_007109.2:g.8328A>G
NG_008418.1:g.1628T>C
NM_000249.3:c.175A>G
NM_000249.4:c.175A>GMANE SELECT
NM_001167617.3:c.-115A>G
NM_001167618.3:c.-549A>G
NM_001167619.3:c.-457A>G
NM_001258271.2:c.175A>G
NM_001258273.2:c.-517+3014A>G
NM_001258274.3:c.-694A>G
NM_001354615.2:c.-452A>G
NM_001354616.2:c.-457A>G
NM_001354617.2:c.-549A>G
NM_001354618.2:c.-549A>G
NM_001354619.2:c.-549A>G
NM_001354620.2:c.-115A>G
NM_001354621.2:c.-642A>G
NM_001354622.2:c.-755A>G
NM_001354623.2:c.-723+2787A>G
NM_001354624.2:c.-652A>G
NM_001354625.2:c.-555A>G
NM_001354626.2:c.-652A>G
NM_001354627.2:c.-652A>G
NM_001354628.2:c.175A>G
NM_001354629.2:c.175A>G
NM_001354630.2:c.175A>G
NP_000240.1:p.Ile59Val
NP_001245200.1:p.Ile59Val
NP_001341557.1:p.Ile59Val
NP_001341558.1:p.Ile59Val
NP_001341559.1:p.Ile59Val
LRG_216t1:c.175A>G
LRG_216:g.8328A>G
NC_000003.11:g.37038168A>G

Protein change:

I59V

Links:

dbSNP: rs2081169952

NCBI 1000 Genomes Browser:

rs2081169952

Molecular consequence:

NM_001167617.3:c.-115A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-549A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-457A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-694A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-452A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-457A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-549A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-549A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-549A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-115A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-642A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-755A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-652A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-555A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-652A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-652A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-517+3014A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2787A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.175A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.175A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.175A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.175A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.175A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004053408	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 16, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004053408

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 16, 2023)

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, SCV004053408.2

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

Description

The p.I59V variant (also known as c.175A>G), located in coding exon 2 of the MLH1 gene, results from an A to G substitution at nucleotide position 175. The isoleucine at codon 59 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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