VCV000090321.2 - ClinVar

NM_000249.4(MLH1):c.677_677+1insT

Germline

Top reviewed classifications are shown here.

Submission summary:

1 submission

1 submitter

1 condition

Reviewed by expert panel

Likely pathogenic

Jun 2019 by International …

for Lynch syndrome

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000249.4(MLH1):c.677_677+1insT

Variation ID: 90321 Accession: VCV000090321.2

Type and length

Insertion, 1 bp

Location

Cytogenetic: 3p22.2 3: 37012099-37012100 (GRCh38) [ NCBI UCSC ] 3: 37053590-37053591 (GRCh37) [ NCBI UCSC ]

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	Oct 1, 2019	Oct 1, 2019	Jun 21, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_000249.4:c.677_677+1insT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_001167617.3:c.383_383+1insT		splice donor
NM_001167618.3:c.-47_-47+1insT		splice donor
NM_001167619.3:c.-47_-47+1insT		splice donor
NM_001258271.2:c.677_677+1insT		splice donor
NM_001258273.2:c.-47_-47+1insT		splice donor
NM_001258274.3:c.-47_-47+1insT		splice donor
NM_001354615.2:c.-47_-47+1insT		splice donor
NM_001354616.2:c.-47_-47+1insT		splice donor
NM_001354617.2:c.-47_-47+1insT		splice donor
NM_001354618.2:c.-47_-47+1insT		splice donor
NM_001354619.2:c.-47_-47+1insT		splice donor
NM_001354620.2:c.383_383+1insT		splice donor
NM_001354621.2:c.-140_-140+1insT		splice donor
NM_001354622.2:c.-253_-253+1insT		splice donor
NM_001354623.2:c.-253_-253+1insT		splice donor
NM_001354624.2:c.-150_-150+1insT		splice donor
NM_001354625.2:c.-150_-150+1insT		splice donor
NM_001354626.2:c.-150_-150+1insT		splice donor
NM_001354627.2:c.-150_-150+1insT		splice donor
NM_001354628.2:c.677_677+1insT		splice donor
NM_001354629.2:c.578_578+1insT		splice donor
NM_001354630.2:c.677_677+1insT		splice donor
NC_000003.12:g.37012099_37012100insT
NC_000003.11:g.37053590_37053591insT
NG_007109.2:g.23750_23751insT
LRG_216:g.23750_23751insT
LRG_216t1:c.677_677+1insT

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000003.12:37012099::T

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

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

dbSNP: rs587779033 ClinGen: CA331099 VarSome

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	5690	5751

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	Likely pathogenic (1)	reviewed by expert panel	Jun 21, 2019	RCV000075812.3

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.
Likely pathogenic (Jun 21, 2019)	reviewed by expert panel (Guidelines v2.4) Method: curation	Lynch syndrome Affected status: yes Allele origin: germline	International Society for Gastrointestinal Hereditary Tumours (InSiGHT) Accession: SCV000106815.3 First in ClinVar: Dec 19, 2013 Last updated: Oct 01, 2019	Other databases http://www.insight-database.org/… http://www.insight-database.org/classifications/?gene=MLH1&variant=c.677_677+1insT Comment: Interrupts canonical donor splice site

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.insight-database.org/classifications/?gene=MLH1&variant=c.677_677+1insT	-	-	-	-

Text-mined citations for rs587779033 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 07, 2023

ClinVar Genomic variation as it relates to human health

NM_000249.4(MLH1):c.677_677+1insT

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs587779033 ...