NM_000249.4(MLH1):c.2210A>T (p.Asp737Val) AND MLH1-related disorder

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 11, 2024
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:: RCV003894921.1

Allele description

NM_000249.4(MLH1):c.2210A>T (p.Asp737Val)

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.2210A>T (p.Asp737Val)

Other names:

p.D737V:GAT>GTT

HGVS:

NC_000003.12:g.37050592A>T
NG_007109.2:g.62243A>T
NM_000249.4:c.2210A>TMANE SELECT
NM_001167617.3:c.1916A>T
NM_001167618.3:c.1487A>T
NM_001167619.3:c.1487A>T
NM_001258271.2:c.2003A>T
NM_001258273.2:c.1487A>T
NM_001258274.3:c.1487A>T
NM_001354615.2:c.1487A>T
NM_001354616.2:c.1487A>T
NM_001354617.2:c.1487A>T
NM_001354618.2:c.1487A>T
NM_001354619.2:c.1487A>T
NM_001354620.2:c.1916A>T
NM_001354621.2:c.1187A>T
NM_001354622.2:c.1187A>T
NM_001354623.2:c.1187A>T
NM_001354624.2:c.1136A>T
NM_001354625.2:c.1136A>T
NM_001354626.2:c.1136A>T
NM_001354627.2:c.1136A>T
NM_001354628.2:c.2117A>T
NM_001354629.2:c.2111A>T
NM_001354630.2:c.2045A>T
NP_000240.1:p.Asp737Val
NP_000240.1:p.Asp737Val
NP_001161089.1:p.Asp639Val
NP_001161090.1:p.Asp496Val
NP_001161091.1:p.Asp496Val
NP_001245200.1:p.Asp668Val
NP_001245202.1:p.Asp496Val
NP_001245203.1:p.Asp496Val
NP_001341544.1:p.Asp496Val
NP_001341545.1:p.Asp496Val
NP_001341546.1:p.Asp496Val
NP_001341547.1:p.Asp496Val
NP_001341548.1:p.Asp496Val
NP_001341549.1:p.Asp639Val
NP_001341550.1:p.Asp396Val
NP_001341551.1:p.Asp396Val
NP_001341552.1:p.Asp396Val
NP_001341553.1:p.Asp379Val
NP_001341554.1:p.Asp379Val
NP_001341555.1:p.Asp379Val
NP_001341556.1:p.Asp379Val
NP_001341557.1:p.Asp706Val
NP_001341558.1:p.Asp704Val
NP_001341559.1:p.Asp682Val
LRG_216t1:c.2210A>T
LRG_216:g.62243A>T
LRG_216p1:p.Asp737Val
NC_000003.11:g.37092083A>T
NM_000249.3:c.2210A>T

Protein change:

D379V

Links:

dbSNP: rs267607885

NCBI 1000 Genomes Browser:

rs267607885

Molecular consequence:

NM_000249.4:c.2210A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.1916A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167618.3:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167619.3:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.2003A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258273.2:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258274.3:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354615.2:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354616.2:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354617.2:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354618.2:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354619.2:c.1487A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.1916A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354621.2:c.1187A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354622.2:c.1187A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354623.2:c.1187A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354624.2:c.1136A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354625.2:c.1136A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354626.2:c.1136A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354627.2:c.1136A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.2117A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.2111A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.2045A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: MLH1-related disorder
Synonyms:: MLH1-related condition
Identifiers:

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Homo sapiens odz, odd Oz/ten-m homolog 1(Drosophila) (ODZ1), mRNA
Homo sapiens odz, odd Oz/ten-m homolog 1(Drosophila) (ODZ1), mRNA
gi|110347399|ref|NM_014253.2|

Nucleotide
Cyanothamnus anemonifolius subsp. anemonifolius voucher NSW 971602 18S ribosomal...
Cyanothamnus anemonifolius subsp. anemonifolius voucher NSW 971602 18S ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and 26S ribosomal RNA gene, partial sequence
gi|1877790030|gb|MN082859.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004714834	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 11, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004714834

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 11, 2024)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004714834.1

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

Description

The MLH1 c.2210A>T variant is predicted to result in the amino acid substitution p.Asp737Val. This variant was reported, along with additional MLH1 variants, in individuals with non-polyposis colorectal cancer (Pagenstecher et al. 2006. PubMed ID: 16341550; Mangold et al. 2005. PubMed ID: 15849733). The significance of these reports is unclear given the uncertainty of the clinical significance of the additional variants and/or the variant phasing. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. In ClinVar, this variant has conflicting interpretations of likely benign and uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/90090/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine