NM_000249.4(MLH1):c.508A>G (p.Ser170Gly) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 22, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000759089.3

Allele description [Variation Report for NM_000249.4(MLH1):c.508A>G (p.Ser170Gly)]

NM_000249.4(MLH1):c.508A>G (p.Ser170Gly)

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.508A>G (p.Ser170Gly)

HGVS:

NC_000003.12:g.37008868A>G
NG_007109.2:g.20519A>G
NM_000249.4:c.508A>GMANE SELECT
NM_001167617.3:c.214A>G
NM_001167618.3:c.-216A>G
NM_001167619.3:c.-179+1805A>G
NM_001258271.2:c.508A>G
NM_001258273.2:c.-216A>G
NM_001258274.3:c.-216A>G
NM_001354615.2:c.-179+1805A>G
NM_001354616.2:c.-179+1805A>G
NM_001354617.2:c.-216A>G
NM_001354618.2:c.-216A>G
NM_001354619.2:c.-216A>G
NM_001354620.2:c.214A>G
NM_001354621.2:c.-309A>G
NM_001354622.2:c.-422A>G
NM_001354623.2:c.-422A>G
NM_001354624.2:c.-319A>G
NM_001354625.2:c.-282+1805A>G
NM_001354626.2:c.-319A>G
NM_001354627.2:c.-319A>G
NM_001354628.2:c.508A>G
NM_001354629.2:c.409A>G
NM_001354630.2:c.508A>G
NP_000240.1:p.Ser170Gly
NP_000240.1:p.Ser170Gly
NP_001161089.1:p.Ser72Gly
NP_001245200.1:p.Ser170Gly
NP_001341549.1:p.Ser72Gly
NP_001341557.1:p.Ser170Gly
NP_001341558.1:p.Ser137Gly
NP_001341559.1:p.Ser170Gly
LRG_216t1:c.508A>G
LRG_216:g.20519A>G
LRG_216p1:p.Ser170Gly
NC_000003.11:g.37050359A>G
NM_000249.3:c.508A>G

Protein change:

S137G

Links:

dbSNP: rs1287294691

NCBI 1000 Genomes Browser:

rs1287294691

Molecular consequence:

NM_001167618.3:c.-216A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-216A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-216A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-216A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-216A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-216A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-309A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-422A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-422A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-319A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-319A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-319A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-179+1805A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354615.2:c.-179+1805A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354616.2:c.-179+1805A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354625.2:c.-282+1805A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.508A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.214A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.508A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.214A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.508A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.409A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.508A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000888189	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Feb 8, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003926032	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 22, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000888189

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Feb 8, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003926032

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 22, 2022)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888189.2

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

#	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

From GeneDx, SCV003926032.1

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22753075)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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