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NM_000249.4(MLH1):c.2140T>C (p.Trp714Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 12, 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:
RCV001014593.3

Allele description [Variation Report for NM_000249.4(MLH1):c.2140T>C (p.Trp714Arg)]

NM_000249.4(MLH1):c.2140T>C (p.Trp714Arg)

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.2140T>C (p.Trp714Arg)
HGVS:
  • NC_000003.12:g.37050522T>C
  • NG_007109.2:g.62173T>C
  • NM_000249.4:c.2140T>CMANE SELECT
  • NM_001167617.3:c.1846T>C
  • NM_001167618.3:c.1417T>C
  • NM_001167619.3:c.1417T>C
  • NM_001258271.2:c.1933T>C
  • NM_001258273.2:c.1417T>C
  • NM_001258274.3:c.1417T>C
  • NM_001354615.2:c.1417T>C
  • NM_001354616.2:c.1417T>C
  • NM_001354617.2:c.1417T>C
  • NM_001354618.2:c.1417T>C
  • NM_001354619.2:c.1417T>C
  • NM_001354620.2:c.1846T>C
  • NM_001354621.2:c.1117T>C
  • NM_001354622.2:c.1117T>C
  • NM_001354623.2:c.1117T>C
  • NM_001354624.2:c.1066T>C
  • NM_001354625.2:c.1066T>C
  • NM_001354626.2:c.1066T>C
  • NM_001354627.2:c.1066T>C
  • NM_001354628.2:c.2047T>C
  • NM_001354629.2:c.2041T>C
  • NM_001354630.2:c.1975T>C
  • NP_000240.1:p.Trp714Arg
  • NP_001161089.1:p.Trp616Arg
  • NP_001161090.1:p.Trp473Arg
  • NP_001161091.1:p.Trp473Arg
  • NP_001245200.1:p.Trp645Arg
  • NP_001245202.1:p.Trp473Arg
  • NP_001245203.1:p.Trp473Arg
  • NP_001341544.1:p.Trp473Arg
  • NP_001341545.1:p.Trp473Arg
  • NP_001341546.1:p.Trp473Arg
  • NP_001341547.1:p.Trp473Arg
  • NP_001341548.1:p.Trp473Arg
  • NP_001341549.1:p.Trp616Arg
  • NP_001341550.1:p.Trp373Arg
  • NP_001341551.1:p.Trp373Arg
  • NP_001341552.1:p.Trp373Arg
  • NP_001341553.1:p.Trp356Arg
  • NP_001341554.1:p.Trp356Arg
  • NP_001341555.1:p.Trp356Arg
  • NP_001341556.1:p.Trp356Arg
  • NP_001341557.1:p.Trp683Arg
  • NP_001341558.1:p.Trp681Arg
  • NP_001341559.1:p.Trp659Arg
  • LRG_216t1:c.2140T>C
  • LRG_216:g.62173T>C
  • NC_000003.11:g.37092013T>C
  • NC_000003.11:g.37092013T>C
  • NM_000249.3:c.2140T>C
Protein change:
W356R
Links:
dbSNP: rs1575639745
NCBI 1000 Genomes Browser:
rs1575639745
Molecular consequence:
  • NM_000249.4:c.2140T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167617.3:c.1846T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167618.3:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167619.3:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258271.2:c.1933T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258273.2:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258274.3:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354615.2:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354616.2:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354617.2:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354618.2:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354619.2:c.1417T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354620.2:c.1846T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354621.2:c.1117T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354622.2:c.1117T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354623.2:c.1117T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354624.2:c.1066T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354625.2:c.1066T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354626.2:c.1066T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354627.2:c.1066T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354628.2:c.2047T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354629.2:c.2041T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354630.2:c.1975T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001175319Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Feb 12, 2024) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV001175319.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.W714R variant (also known as c.2140T>C), located in coding exon 19 of the MLH1 gene, results from a T to C substitution at nucleotide position 2140. The tryptophan at codon 714 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024