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NM_000249.4(MLH1):c.546-5del AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Sep 21, 2023
Review status:
criteria provided, conflicting classifications
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:
RCV001705513.5

Allele description [Variation Report for NM_000249.4(MLH1):c.546-5del]

NM_000249.4(MLH1):c.546-5del

Gene:
MLH1:mutL homolog 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
3p22.2
Genomic location:
Preferred name:
NM_000249.4(MLH1):c.546-5del
HGVS:
  • NC_000003.12:g.37011815del
  • NG_007109.2:g.23466del
  • NM_000249.4:c.546-5delMANE SELECT
  • NM_001167617.3:c.252-5del
  • NM_001167618.3:c.-178-5del
  • NM_001167619.3:c.-178-5del
  • NM_001258271.2:c.546-5del
  • NM_001258273.2:c.-178-5del
  • NM_001258274.3:c.-178-5del
  • NM_001354615.2:c.-178-5del
  • NM_001354616.2:c.-178-5del
  • NM_001354617.2:c.-178-5del
  • NM_001354618.2:c.-178-5del
  • NM_001354619.2:c.-178-5del
  • NM_001354620.2:c.252-5del
  • NM_001354621.2:c.-271-5del
  • NM_001354622.2:c.-384-5del
  • NM_001354623.2:c.-384-5del
  • NM_001354624.2:c.-281-5del
  • NM_001354625.2:c.-281-5del
  • NM_001354626.2:c.-281-5del
  • NM_001354627.2:c.-281-5del
  • NM_001354628.2:c.546-5del
  • NM_001354629.2:c.447-5del
  • NM_001354630.2:c.546-5del
  • LRG_216t1:c.546-5del
  • LRG_216:g.23466del
  • NC_000003.11:g.37053303del
  • NC_000003.11:g.37053306del
  • NM_000249.3:c.546-5del
  • NM_000249.3:c.546-5del
  • NM_000249.3:c.546-5delT
Links:
dbSNP: rs1553643965
NCBI 1000 Genomes Browser:
rs1553643965
Molecular consequence:
  • NM_000249.4:c.546-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001167617.3:c.252-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001167618.3:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001167619.3:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001258271.2:c.546-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001258273.2:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001258274.3:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354615.2:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354616.2:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354617.2:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354618.2:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354619.2:c.-178-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354620.2:c.252-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354621.2:c.-271-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354622.2:c.-384-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354623.2:c.-384-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354624.2:c.-281-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354625.2:c.-281-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354626.2:c.-281-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354627.2:c.-281-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354628.2:c.546-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354629.2:c.447-5del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354630.2:c.546-5del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000571207GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Likely benign
(Nov 10, 2022)
germlineclinical testing

Citation Link,

SCV004220891Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)
Uncertain significance
(Sep 21, 2023)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000571207.6

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

Description

See Variant Classification Assertion Criteria.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220891.1

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

Description

To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/251150 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect MLH1 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Sep 29, 2024