NM_000249.4(MLH1):c.206G>A (p.Arg69Lys) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 10, 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:: RCV000692100.13

Allele description [Variation Report for NM_000249.4(MLH1):c.206G>A (p.Arg69Lys)]

NM_000249.4(MLH1):c.206G>A (p.Arg69Lys)

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.206G>A (p.Arg69Lys)

HGVS:

NC_000003.12:g.36996708G>A
NG_007109.2:g.8359G>A
NG_008418.1:g.1597C>T
NM_000249.4:c.206G>AMANE SELECT
NM_001167617.3:c.-84G>A
NM_001167618.3:c.-518G>A
NM_001167619.3:c.-426G>A
NM_001258271.2:c.206G>A
NM_001258273.2:c.-517+3045G>A
NM_001258274.3:c.-663G>A
NM_001354615.2:c.-421G>A
NM_001354616.2:c.-426G>A
NM_001354617.2:c.-518G>A
NM_001354618.2:c.-518G>A
NM_001354619.2:c.-518G>A
NM_001354620.2:c.-84G>A
NM_001354621.2:c.-611G>A
NM_001354622.2:c.-724G>A
NM_001354623.2:c.-723+2818G>A
NM_001354624.2:c.-621G>A
NM_001354625.2:c.-524G>A
NM_001354626.2:c.-621G>A
NM_001354627.2:c.-621G>A
NM_001354628.2:c.206G>A
NM_001354629.2:c.206G>A
NM_001354630.2:c.206G>A
NP_000240.1:p.Arg69Lys
NP_000240.1:p.Arg69Lys
NP_001245200.1:p.Arg69Lys
NP_001341557.1:p.Arg69Lys
NP_001341558.1:p.Arg69Lys
NP_001341559.1:p.Arg69Lys
LRG_216t1:c.206G>A
LRG_216:g.8359G>A
LRG_216p1:p.Arg69Lys
NC_000003.11:g.37038199G>A
NM_000249.3:c.206G>A

Protein change:

R69K

Links:

dbSNP: rs63751661

NCBI 1000 Genomes Browser:

rs63751661

Molecular consequence:

NM_001167617.3:c.-84G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-518G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-426G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-663G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-421G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-426G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-518G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-518G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-518G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-84G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-611G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-724G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-621G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-524G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-621G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-621G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-517+3045G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2818G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

Recent activity

Clear Turn Off Turn On

protein DETOXIFICATION 16 [Cucumis sativus]
protein DETOXIFICATION 16 [Cucumis sativus]
gi|778656437|ref|XP_004137332.2|

Protein
PREDICTED: uncharacterized protein LOC103501777 isoform X2 [Cucumis melo]
PREDICTED: uncharacterized protein LOC103501777 isoform X2 [Cucumis melo]
gi|659127417|ref|XP_008463691.1|

Protein
protein CHAPERONE-LIKE PROTEIN OF POR1, chloroplastic [Cucumis melo]
protein CHAPERONE-LIKE PROTEIN OF POR1, chloroplastic [Cucumis melo]
gi|659106470|ref|XP_008453340.1|

Protein
probable auxin efflux carrier component 1c [Cucurbita pepo subsp. pepo]
probable auxin efflux carrier component 1c [Cucurbita pepo subsp. pepo]
gi|1333176349|ref|XP_023519167.1|

Protein
putative root meristem growth factor 8 [Cucumis melo var. makuwa]
putative root meristem growth factor 8 [Cucumis melo var. makuwa]
gi|1735191754|gb|KAA0034486.1||gnl| STE|E6C27_scaffold65G004980

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000819908	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 10, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21520333, 11555625, 17510385, 31697235, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000819908

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 10, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

LOVD v.2.0: the next generation in gene variant databases.

Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT.

Hum Mutat. 2011 May;32(5):557-63. doi: 10.1002/humu.21438. Epub 2011 Feb 22.

PubMed [citation]

PMID:: 21520333

Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae.

Ellison AR, Lofing J, Bitter GA.

Hum Mol Genet. 2001 Sep 1;10(18):1889-900.

PubMed [citation]

PMID:: 11555625

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819908.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 69 of the MLH1 protein (p.Arg69Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of MLH1-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 489896). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on MLH1 function (PMID: 11555625, 17510385, 31697235). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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: Nov 10, 2024

ClinVar

Relating variation to medicine