NM_000249.4(MLH1):c.895A>G (p.Ser299Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 19, 2015
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:: RCV000217994.3

Allele description [Variation Report for NM_000249.4(MLH1):c.895A>G (p.Ser299Gly)]

NM_000249.4(MLH1):c.895A>G (p.Ser299Gly)

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.895A>G (p.Ser299Gly)

HGVS:

NC_000003.12:g.37020320A>G
NG_007109.2:g.31971A>G
NM_000249.4:c.895A>GMANE SELECT
NM_001167617.3:c.601A>G
NM_001167618.3:c.172A>G
NM_001167619.3:c.172A>G
NM_001258271.2:c.895A>G
NM_001258273.2:c.172A>G
NM_001258274.3:c.172A>G
NM_001354615.2:c.172A>G
NM_001354616.2:c.172A>G
NM_001354617.2:c.172A>G
NM_001354618.2:c.172A>G
NM_001354619.2:c.172A>G
NM_001354620.2:c.601A>G
NM_001354621.2:c.-129A>G
NM_001354622.2:c.-129A>G
NM_001354623.2:c.-129A>G
NM_001354624.2:c.-36-5317A>G
NM_001354625.2:c.-36-5317A>G
NM_001354626.2:c.-36-5317A>G
NM_001354627.2:c.-36-5317A>G
NM_001354628.2:c.895A>G
NM_001354629.2:c.796A>G
NM_001354630.2:c.895A>G
NP_000240.1:p.Ser299Gly
NP_000240.1:p.Ser299Gly
NP_001161089.1:p.Ser201Gly
NP_001161090.1:p.Ser58Gly
NP_001161091.1:p.Ser58Gly
NP_001245200.1:p.Ser299Gly
NP_001245202.1:p.Ser58Gly
NP_001245203.1:p.Ser58Gly
NP_001341544.1:p.Ser58Gly
NP_001341545.1:p.Ser58Gly
NP_001341546.1:p.Ser58Gly
NP_001341547.1:p.Ser58Gly
NP_001341548.1:p.Ser58Gly
NP_001341549.1:p.Ser201Gly
NP_001341557.1:p.Ser299Gly
NP_001341558.1:p.Ser266Gly
NP_001341559.1:p.Ser299Gly
LRG_216t1:c.895A>G
LRG_216:g.31971A>G
LRG_216p1:p.Ser299Gly
NC_000003.11:g.37061811A>G
NM_000249.3:c.895A>G

Protein change:

S201G

Links:

dbSNP: rs876658827

NCBI 1000 Genomes Browser:

rs876658827

Molecular consequence:

NM_001354621.2:c.-129A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-129A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-129A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-36-5317A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354625.2:c.-36-5317A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354626.2:c.-36-5317A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354627.2:c.-36-5317A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.895A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.601A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001167618.3:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001167619.3:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.895A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258273.2:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258274.3:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354615.2:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354616.2:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354617.2:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354618.2:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354619.2:c.172A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.601A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.895A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.796A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.895A>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
SCV000274578	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 19, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000274578

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 19, 2015)

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, SCV000274578.7

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

Description

The p.S299G variant (also known as c.895A>G), located in coding exon 11 of the MLH1 gene, results from an A to G substitution at nucleotide position 895. The serine at codon 299 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 42000 alleles tested) in our clinical cohort. This amino acid position is not 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 p.S299G 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: May 1, 2024

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