NM_000249.4(MLH1):c.188A>G (p.Asp63Gly) AND not specified

Germline classification:: Uncertain significance (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:: RCV001553746.1

Allele description [Variation Report for NM_000249.4(MLH1):c.188A>G (p.Asp63Gly)]

NM_000249.4(MLH1):c.188A>G (p.Asp63Gly)

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.188A>G (p.Asp63Gly)

HGVS:

NC_000003.12:g.36996690A>G
NG_007109.2:g.8341A>G
NG_008418.1:g.1615T>C
NM_000249.4:c.188A>GMANE SELECT
NM_001167617.3:c.-102A>G
NM_001167618.3:c.-536A>G
NM_001167619.3:c.-444A>G
NM_001258271.2:c.188A>G
NM_001258273.2:c.-517+3027A>G
NM_001258274.3:c.-681A>G
NM_001354615.2:c.-439A>G
NM_001354616.2:c.-444A>G
NM_001354617.2:c.-536A>G
NM_001354618.2:c.-536A>G
NM_001354619.2:c.-536A>G
NM_001354620.2:c.-102A>G
NM_001354621.2:c.-629A>G
NM_001354622.2:c.-742A>G
NM_001354623.2:c.-723+2800A>G
NM_001354624.2:c.-639A>G
NM_001354625.2:c.-542A>G
NM_001354626.2:c.-639A>G
NM_001354627.2:c.-639A>G
NM_001354628.2:c.188A>G
NM_001354629.2:c.188A>G
NM_001354630.2:c.188A>G
NP_000240.1:p.Asp63Gly
NP_000240.1:p.Asp63Gly
NP_001245200.1:p.Asp63Gly
NP_001341557.1:p.Asp63Gly
NP_001341558.1:p.Asp63Gly
NP_001341559.1:p.Asp63Gly
LRG_216t1:c.188A>G
LRG_216:g.8341A>G
LRG_216p1:p.Asp63Gly
NC_000003.11:g.37038181A>G
NM_000249.3:c.188A>G

Protein change:

D63G

Links:

dbSNP: rs1064795693

NCBI 1000 Genomes Browser:

rs1064795693

Molecular consequence:

NM_001167617.3:c.-102A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-536A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-444A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-681A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-439A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-444A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-536A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-536A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-536A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-102A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-629A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-742A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-639A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-542A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-639A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-639A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-517+3027A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2800A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.188A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.188A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.188A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.188A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.188A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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Congenital myasthenic syndrome 4A
Congenital myasthenic syndrome 4A

MedGen
C4225413[conceptid] (1)
MedGen
Blastomyces gilchristii SLH14081 C2H2 finger domain-containing protein (BDBG_000...
Blastomyces gilchristii SLH14081 C2H2 finger domain-containing protein (BDBG_00015), mRNA
gi|1778678935|ref|XM_031719691.1|

Nucleotide
nsv569979 (1)
dbVar
ATP-sensitive inward rectifier potassium channel 15 isoform a [Mus musculus]
ATP-sensitive inward rectifier potassium channel 15 isoform a [Mus musculus]
gi|411147352|ref|NP_001258621.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001774736	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 7, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001774736

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001774736.1

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

Description

Variant summary: MLH1 c.188A>G (p.Asp63Gly) results in a non-conservative amino acid change located in the DNA mismatch repair protein family, N-terminal domain (IPR002099) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251442 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.188A>G in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Oct 8, 2024

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