VCV000617615.1 - ClinVar

NM_000249.3(MLH1):c.512_513insAlu

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000249.3(MLH1):c.512_513insAlu

Variation ID: 617615 Accession: VCV000617615.1

Type and length

Insertion, -

Location

Cytogenetic: 3p22.2 -

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 8, 2019	Feb 8, 2019	May 23, 2018

HGVS

Protein change

Other names

NM_000249.3:c.512_513insAlu

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

exon loss; Variation Ontology [ VariO:0381]

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MLH1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	5694	5755

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Lynch syndrome 1	Pathogenic (1)	criteria provided, single submitter	May 23, 2018	RCV000754776.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 23, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing, in vivo	Lynch syndrome 1 (Autosomal dominant inheritance) Affected status: yes, not applicable Allele origin: germline, not applicable	Biologie des Tumeurs Solides, CHU de Montpellier Accession: SCV000864261.1 First in ClinVar: Feb 08, 2019 Last updated: Feb 08, 2019	Comment: This variant was identified in 3 DNA samples from patients with Lynch syndrome in the same family. It was not detected in an unaffected member's … (more) This variant was identified in 3 DNA samples from patients with Lynch syndrome in the same family. It was not detected in an unaffected member's DNA sample from the same family. (less) Observation 1: Number of individuals with the variant: 3 Age: 33-58 years Sex: mixed Ethnicity/Population group: Caucasian Geographic origin: France Observation 2: Sex: mixed Tissue: Blood Comment on evidence: Semiquantitative RT-PCR analysis showed that this mutation leads to a frameshift deletion of MLH1 exon 6 and a predicted truncated protein p.(Glu153Phefs8). This aberrant transcripts … (more) Semiquantitative RT-PCR analysis showed that this mutation leads to a frameshift deletion of MLH1 exon 6 and a predicted truncated protein p.(Glu153Phefs8). This aberrant transcripts are in the majority. (less)

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
exon loss	Method not provided	Result not provided	Biologie des Tumeurs Solides, CHU de Montpellier Accession: SCV000864261.1

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Jun 10, 2024

ClinVar Genomic variation as it relates to human health

NM_000249.3(MLH1):c.512_513insAlu

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...