Variant summary: MSH6 c.2415_2418delinsTTCT results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 245264 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2415_2418delinsTTCT in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.2415_2418delinsTTCT (p.Ile805_Ser806=)
Germline
Classification
Help
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)
Help
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.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000179.3(MSH6):c.2415_2418delinsTTCT (p.Ile805_Ser806=)
Variation ID: 928979 Accession: VCV000928979.1
- Type and length
-
Indel, 4 bp
- Location
-
Cytogenetic: 2p16.3 2: 47800398-47800401 (GRCh38) [ NCBI UCSC ] 2: 48027537-48027540 (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 Jun 22, 2020 Jun 22, 2020 Mar 1, 2019 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.2415_2418delinsTTCT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Ile805_Ser806= synonymous NM_000179.2:c.2415_2418delCTCCinsTTCT NP_000170.1:p.Ile805_Ser806= synonymous NM_001281492.2:c.2025_2028delinsTTCT NP_001268421.1:p.Ile675_Ser676= synonymous NM_001281493.2:c.1509_1512delinsTTCT NP_001268422.1:p.Ile503_Ser504= synonymous NM_001281494.2:c.1509_1512delinsTTCT NP_001268423.1:p.Ile503_Ser504= synonymous NM_001406795.1:c.2511_2514delinsTTCT NP_001393724.1:p.Ile837_Ser838= synonymous NM_001406796.1:c.2415_2418delinsTTCT NP_001393725.1:p.Ile805_Ser806= synonymous NM_001406797.1:c.2118_2121delinsTTCT NP_001393726.1:p.Ile706_Ser707= synonymous NM_001406798.1:c.2415_2418delinsTTCT NP_001393727.1:p.Ile805_Ser806= synonymous NM_001406799.1:c.1890_1893delinsTTCT NP_001393728.1:p.Ile630_Ser631= synonymous NM_001406800.1:c.2415_2418delinsTTCT NP_001393729.1:p.Ile805_Ser806= synonymous NM_001406801.1:c.2118_2121delinsTTCT NP_001393730.1:p.Ile706_Ser707= synonymous NM_001406802.1:c.2511_2514delinsTTCT NP_001393731.1:p.Ile837_Ser838= synonymous NM_001406803.1:c.2308+107_2308+110delinsTTCT intron variant NM_001406804.1:c.2337_2340delinsTTCT NP_001393733.1:p.Ile779_Ser780= synonymous NM_001406805.1:c.2118_2121delinsTTCT NP_001393734.1:p.Ile706_Ser707= synonymous NM_001406806.1:c.1890_1893delinsTTCT NP_001393735.1:p.Ile630_Ser631= synonymous NM_001406807.1:c.1890_1893delinsTTCT NP_001393736.1:p.Ile630_Ser631= synonymous NM_001406808.1:c.2415_2418delinsTTCT NP_001393737.1:p.Ile805_Ser806= synonymous NM_001406809.1:c.2415_2418delinsTTCT NP_001393738.1:p.Ile805_Ser806= synonymous NM_001406811.1:c.1509_1512delinsTTCT NP_001393740.1:p.Ile503_Ser504= synonymous NM_001406812.1:c.1509_1512delinsTTCT NP_001393741.1:p.Ile503_Ser504= synonymous NM_001406813.1:c.2421_2424delinsTTCT NP_001393742.1:p.Ile807_Ser808= synonymous NM_001406814.1:c.1509_1512delinsTTCT NP_001393743.1:p.Ile503_Ser504= synonymous NM_001406815.1:c.1509_1512delinsTTCT NP_001393744.1:p.Ile503_Ser504= synonymous NM_001406816.1:c.1509_1512delinsTTCT NP_001393745.1:p.Ile503_Ser504= synonymous NM_001406817.1:c.1606+809_1606+812delinsTTCT intron variant NM_001406818.1:c.2118_2121delinsTTCT NP_001393747.1:p.Ile706_Ser707= synonymous NM_001406819.1:c.2118_2121delinsTTCT NP_001393748.1:p.Ile706_Ser707= synonymous NM_001406820.1:c.2118_2121delinsTTCT NP_001393749.1:p.Ile706_Ser707= synonymous NM_001406821.1:c.2118_2121delinsTTCT NP_001393750.1:p.Ile706_Ser707= synonymous NM_001406822.1:c.2118_2121delinsTTCT NP_001393751.1:p.Ile706_Ser707= synonymous NM_001406823.1:c.1509_1512delinsTTCT NP_001393752.1:p.Ile503_Ser504= synonymous NM_001406824.1:c.2118_2121delinsTTCT NP_001393753.1:p.Ile706_Ser707= synonymous NM_001406825.1:c.2118_2121delinsTTCT NP_001393754.1:p.Ile706_Ser707= synonymous NM_001406826.1:c.2247_2250delinsTTCT NP_001393755.1:p.Ile749_Ser750= synonymous NM_001406827.1:c.2118_2121delinsTTCT NP_001393756.1:p.Ile706_Ser707= synonymous NM_001406828.1:c.2118_2121delinsTTCT NP_001393757.1:p.Ile706_Ser707= synonymous NM_001406829.1:c.1509_1512delinsTTCT NP_001393758.1:p.Ile503_Ser504= synonymous NM_001406830.1:c.2118_2121delinsTTCT NP_001393759.1:p.Ile706_Ser707= synonymous NM_001407362.1:c.628-268_628-265delinsTTCT intron variant NR_176256.1:n.1277_1280delinsTTCT non-coding transcript variant NR_176257.1:n.2504_2507delinsTTCT non-coding transcript variant NR_176258.1:n.2504_2507delinsTTCT non-coding transcript variant NR_176259.1:n.2504_2507delinsTTCT non-coding transcript variant NR_176261.1:n.2504_2507delinsTTCT non-coding transcript variant NC_000002.12:g.47800398_47800401delinsTTCT NC_000002.11:g.48027537_48027540delinsTTCT NG_007111.1:g.22252_22255delinsTTCT LRG_219:g.22252_22255delinsTTCT LRG_219t1:c.2415_2418delinsTTCT - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000002.12:47800397:CTCC:TTCT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| MSH6 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9161 | 9479 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 1, 2019 | RCV001193701.1 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Mar 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362735.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: MSH6 c.2415_2418delinsTTCT results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to … (more)
Variant summary: MSH6 c.2415_2418delinsTTCT results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 245264 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2415_2418delinsTTCT in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. (less)
|
Comment:
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. |
Comment:
Variant summary: MSH6 c.2415_2418delinsTTCT results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 245264 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2415_2418delinsTTCT in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Citations for germline classification of this variant
Help| 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 rs1669459551 ...
HelpThese 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 Apr 23, 2023
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.