U.S. flag

An official website of the United States government

NM_000249.4(MLH1):c.653C>T (p.Ser218Phe) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 20, 2019
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:
RCV001057623.6

Allele description [Variation Report for NM_000249.4(MLH1):c.653C>T (p.Ser218Phe)]

NM_000249.4(MLH1):c.653C>T (p.Ser218Phe)

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.653C>T (p.Ser218Phe)
HGVS:
  • NC_000003.12:g.37012075C>T
  • NG_007109.2:g.23726C>T
  • NM_000249.4:c.653C>TMANE SELECT
  • NM_001167617.3:c.359C>T
  • NM_001167618.3:c.-71C>T
  • NM_001167619.3:c.-71C>T
  • NM_001258271.2:c.653C>T
  • NM_001258273.2:c.-71C>T
  • NM_001258274.3:c.-71C>T
  • NM_001354615.2:c.-71C>T
  • NM_001354616.2:c.-71C>T
  • NM_001354617.2:c.-71C>T
  • NM_001354618.2:c.-71C>T
  • NM_001354619.2:c.-71C>T
  • NM_001354620.2:c.359C>T
  • NM_001354621.2:c.-164C>T
  • NM_001354622.2:c.-277C>T
  • NM_001354623.2:c.-277C>T
  • NM_001354624.2:c.-174C>T
  • NM_001354625.2:c.-174C>T
  • NM_001354626.2:c.-174C>T
  • NM_001354627.2:c.-174C>T
  • NM_001354628.2:c.653C>T
  • NM_001354629.2:c.554C>T
  • NM_001354630.2:c.653C>T
  • NP_000240.1:p.Ser218Phe
  • NP_001161089.1:p.Ser120Phe
  • NP_001245200.1:p.Ser218Phe
  • NP_001341549.1:p.Ser120Phe
  • NP_001341557.1:p.Ser218Phe
  • NP_001341558.1:p.Ser185Phe
  • NP_001341559.1:p.Ser218Phe
  • LRG_216t1:c.653C>T
  • LRG_216:g.23726C>T
  • NC_000003.11:g.37053566C>T
  • NM_000249.3:c.653C>T
Protein change:
S120F
Links:
dbSNP: rs2082350729
NCBI 1000 Genomes Browser:
rs2082350729
Molecular consequence:
  • NM_001167618.3:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001167619.3:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258273.2:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001258274.3:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354615.2:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354616.2:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354617.2:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354618.2:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354619.2:c.-71C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354621.2:c.-164C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354622.2:c.-277C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354623.2:c.-277C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354624.2:c.-174C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354625.2:c.-174C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354626.2:c.-174C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354627.2:c.-174C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000249.4:c.653C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167617.3:c.359C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258271.2:c.653C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354620.2:c.359C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354628.2:c.653C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354629.2:c.554C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354630.2:c.653C>T - 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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001222126Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 20, 2019) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001222126.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces serine with phenylalanine at codon 218 of the MLH1 protein (p.Ser218Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MLH1-related conditions. This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Sep 29, 2024