NM_000249.4(MLH1):c.1852_1853delinsGC (p.Lys618Ala) AND not specified

Germline classification:: Benign/Likely benign (8 submissions)
Last evaluated:: May 27, 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:: RCV000121363.31

Allele description [Variation Report for NM_000249.4(MLH1):c.1852_1853delinsGC (p.Lys618Ala)]

NM_000249.4(MLH1):c.1852_1853delinsGC (p.Lys618Ala)

Gene:

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

Variant type:

Indel

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.1852_1853delinsGC (p.Lys618Ala)

HGVS:

NC_000003.12:g.37047639_37047640delinsGC
NG_007109.2:g.59290_59291delinsGC
NM_000249.4:c.1852_1853delinsGCMANE SELECT
NM_001167617.3:c.1558_1559delinsGC
NM_001167618.3:c.1129_1130delinsGC
NM_001167619.3:c.1129_1130delinsGC
NM_001258271.2:c.1852_1853delinsGC
NM_001258273.2:c.1129_1130delinsGC
NM_001258274.3:c.1129_1130delinsGC
NM_001354615.2:c.1129_1130delinsGC
NM_001354616.2:c.1129_1130delinsGC
NM_001354617.2:c.1129_1130delinsGC
NM_001354618.2:c.1129_1130delinsGC
NM_001354619.2:c.1129_1130delinsGC
NM_001354620.2:c.1558_1559delinsGC
NM_001354621.2:c.829_830delinsGC
NM_001354622.2:c.829_830delinsGC
NM_001354623.2:c.829_830delinsGC
NM_001354624.2:c.778_779delinsGC
NM_001354625.2:c.778_779delinsGC
NM_001354626.2:c.778_779delinsGC
NM_001354627.2:c.778_779delinsGC
NM_001354628.2:c.1852_1853delinsGC
NM_001354629.2:c.1753_1754delinsGC
NM_001354630.2:c.1732-878_1732-877delinsGC
NP_000240.1:p.Lys618Ala
NP_001161089.1:p.Lys520Ala
NP_001161090.1:p.Lys377Ala
NP_001161091.1:p.Lys377Ala
NP_001245200.1:p.Lys618Ala
NP_001245202.1:p.Lys377Ala
NP_001245203.1:p.Lys377Ala
NP_001341544.1:p.Lys377Ala
NP_001341545.1:p.Lys377Ala
NP_001341546.1:p.Lys377Ala
NP_001341547.1:p.Lys377Ala
NP_001341548.1:p.Lys377Ala
NP_001341549.1:p.Lys520Ala
NP_001341550.1:p.Lys277Ala
NP_001341551.1:p.Lys277Ala
NP_001341552.1:p.Lys277Ala
NP_001341553.1:p.Lys260Ala
NP_001341554.1:p.Lys260Ala
NP_001341555.1:p.Lys260Ala
NP_001341556.1:p.Lys260Ala
NP_001341557.1:p.Lys618Ala
NP_001341558.1:p.Lys585Ala
LRG_216:g.59290_59291delinsGC
NC_000003.11:g.37089130_37089131delinsGC
NM_000249.3:c.1852_1853delAAinsGC
NM_000249.4:c.1852_1853delinsGC
NM_001354630.1:c.1732-878_1732-877delinsGC
p.K618A

Protein change:

K260A; LYS618ALA

Links:

OMIM: 120436.0012; dbSNP: rs35502531

NCBI 1000 Genomes Browser:

rs35502531

Molecular consequence:

NM_001354630.2:c.1732-878_1732-877delinsGC - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.1852_1853delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.1558_1559delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001167618.3:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001167619.3:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.1852_1853delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001258273.2:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001258274.3:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354615.2:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354616.2:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354617.2:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354618.2:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354619.2:c.1129_1130delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.1558_1559delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354621.2:c.829_830delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354622.2:c.829_830delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354623.2:c.829_830delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354624.2:c.778_779delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354625.2:c.778_779delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354626.2:c.778_779delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354627.2:c.778_779delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.1852_1853delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.1753_1754delinsGC - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000085544	ITMI	no classification provided	not provided	germline	reference population	PubMed (1) [See all records that cite this PMID]
SCV000257068	Mayo Clinic Laboratories, Mayo Clinic	no assertion criteria provided	Uncertain significance	unknown	research
SCV000601370	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Benign (May 31, 2021)	unknown	clinical testing	PubMed (14) [See all records that cite these PMIDs] 27247567, 31784484, 31697235, 15300854, 18325052, 21247423, 24743384, 22753075, 19669161, 22949379, 16083711, 17510385, 18205192, 26467025
SCV000805957	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jan 13, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001906390	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001964011	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV002070700	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Nov 29, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005197408	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (May 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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	unknown	unknown	3	not provided	not provided	not provided	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
African	germline	unknown	not provided	not provided	not provided	43	not provided	reference population
African_European	germline	unknown	not provided	not provided	not provided	46	not provided	reference population
Central_Asian	germline	unknown	not provided	not provided	not provided	50	not provided	reference population
East_Asian	germline	unknown	not provided	not provided	not provided	62	not provided	reference population
European	germline	unknown	not provided	not provided	not provided	331	not provided	reference population
Hispanic	germline	unknown	not provided	not provided	not provided	118	not provided	reference population
Whole_cohort	germline	unknown	not provided	not provided	not provided	681	not provided	reference population

Citations

PubMed

Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

Bodian DL, McCutcheon JN, Kothiyal P, Huddleston KC, Iyer RK, Vockley JG, Niederhuber JE.

PLoS One. 2014;9(4):e94554. doi: 10.1371/journal.pone.0094554.

PubMed [citation]

PMID:: 24728327
PMCID:: PMC3984285

Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome.

Moreno-Ortiz JM, Ayala-Madrigal Mde L, Corona-Rivera JR, Centeno-Flores M, Maciel-Gutiérrez V, Franco-Topete RA, Armendáriz-Borunda J, Hotchkiss E, Pérez-Carbonell L, Rhees J, Boland CR, Gutiérrez-Angulo M.

Gastroenterol Res Pract. 2016;2016:5278024. doi: 10.1155/2016/5278024. Epub 2016 May 10.

PubMed [citation]

PMID:: 27247567
PMCID:: PMC4877485

See all PubMed Citations (16)

Details of each submission

From ITMI, SCV000085544.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	African	not provided	not provided	not provided	reference population	PubMed (1)
2	African_European	not provided	not provided	not provided	reference population	PubMed (1)
3	Central_Asian	not provided	not provided	not provided	reference population	PubMed (1)
4	East_Asian	not provided	not provided	not provided	reference population	PubMed (1)
5	European	not provided	not provided	not provided	reference population	PubMed (1)
6	Hispanic	not provided	not provided	not provided	reference population	PubMed (1)
7	Whole_cohort	not provided	not provided	not provided	reference population	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	43	not provided	discovery		not provided	0	not provided	not provided
2	germline	unknown	46	not provided	discovery		not provided	0	not provided	not provided
3	germline	unknown	50	not provided	discovery		not provided	0	not provided	not provided
4	germline	unknown	62	not provided	discovery		not provided	0	not provided	not provided
5	germline	unknown	331	not provided	discovery		not provided	0.0015	not provided	not provided
6	germline	unknown	118	not provided	discovery		not provided	0.0085	not provided	not provided
7	germline	unknown	681	not provided	discovery		not provided	0.0022	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV000257068.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		3	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601370.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (14)

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

From PreventionGenetics, part of Exact Sciences, SCV000805957.1

#	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 Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus, SCV001906390.1

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

#	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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001964011.1

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

#	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

From Genetic Services Laboratory, University of Chicago, SCV002070700.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005197408.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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