ClinVar Genomic variation as it relates to human health
NM_001376571.1(MADD):c.2996C>T (p.Pro999Leu)
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.
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(2); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001376571.1(MADD):c.2996C>T (p.Pro999Leu)
Variation ID: 2345004 Accession: VCV002345004.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p11.2 11: 47290046 (GRCh38) [ NCBI UCSC ] 11: 47311597 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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, 2023 Aug 11, 2024 May 8, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001376571.1:c.2996C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001363500.1:p.Pro999Leu missense NM_001135943.2:c.2807C>T NP_001129415.1:p.Pro936Leu missense NM_001135944.2:c.2807C>T NP_001129416.1:p.Pro936Leu missense NM_001376572.1:c.2996C>T NP_001363501.1:p.Pro999Leu missense NM_001376573.1:c.2996C>T NP_001363502.1:p.Pro999Leu missense NM_001376574.1:c.2996C>T NP_001363503.1:p.Pro999Leu missense NM_001376575.1:c.2936C>T NP_001363504.1:p.Pro979Leu missense NM_001376576.1:c.2936C>T NP_001363505.1:p.Pro979Leu missense NM_001376577.1:c.2936C>T NP_001363506.1:p.Pro979Leu missense NM_001376578.1:c.2909C>T NP_001363507.1:p.Pro970Leu missense NM_001376579.1:c.2936C>T NP_001363508.1:p.Pro979Leu missense NM_001376580.1:c.2936C>T NP_001363509.1:p.Pro979Leu missense NM_001376581.1:c.2867C>T NP_001363510.1:p.Pro956Leu missense NM_001376582.1:c.2867C>T NP_001363511.1:p.Pro956Leu missense NM_001376583.1:c.2834C>T NP_001363512.1:p.Pro945Leu missense NM_001376584.1:c.2936C>T NP_001363513.1:p.Pro979Leu missense NM_001376585.1:c.2807C>T NP_001363514.1:p.Pro936Leu missense NM_001376586.1:c.2867C>T NP_001363515.1:p.Pro956Leu missense NM_001376593.1:c.2936C>T NP_001363522.1:p.Pro979Leu missense NM_001376594.1:c.2936C>T NP_001363523.1:p.Pro979Leu missense NM_001376595.1:c.2807C>T NP_001363524.1:p.Pro936Leu missense NM_001376596.1:c.3014C>T NP_001363525.1:p.Pro1005Leu missense NM_001376597.1:c.2807C>T NP_001363526.1:p.Pro936Leu missense NM_001376598.1:c.2807C>T NP_001363527.1:p.Pro936Leu missense NM_001376599.1:c.2996C>T NP_001363528.1:p.Pro999Leu missense NM_001376600.1:c.2996C>T NP_001363529.1:p.Pro999Leu missense NM_001376601.1:c.2996C>T NP_001363530.1:p.Pro999Leu missense NM_001376602.1:c.2843C>T NP_001363531.1:p.Pro948Leu missense NM_001376603.1:c.2807C>T NP_001363532.1:p.Pro936Leu missense NM_001376604.1:c.2807C>T NP_001363533.1:p.Pro936Leu missense NM_001376605.1:c.2996C>T NP_001363534.1:p.Pro999Leu missense NM_001376606.1:c.2996C>T NP_001363535.1:p.Pro999Leu missense NM_001376607.1:c.2867C>T NP_001363536.1:p.Pro956Leu missense NM_001376608.1:c.2936C>T NP_001363537.1:p.Pro979Leu missense NM_001376609.1:c.2996C>T NP_001363538.1:p.Pro999Leu missense NM_001376610.1:c.2936C>T NP_001363539.1:p.Pro979Leu missense NM_001376611.1:c.2834C>T NP_001363540.1:p.Pro945Leu missense NM_001376612.1:c.2936C>T NP_001363541.1:p.Pro979Leu missense NM_001376613.1:c.2834C>T NP_001363542.1:p.Pro945Leu missense NM_001376614.1:c.2834C>T NP_001363543.1:p.Pro945Leu missense NM_001376615.1:c.2807C>T NP_001363544.1:p.Pro936Leu missense NM_001376616.1:c.2807C>T NP_001363545.1:p.Pro936Leu missense NM_001376617.1:c.2867C>T NP_001363546.1:p.Pro956Leu missense NM_001376618.1:c.2807C>T NP_001363547.1:p.Pro936Leu missense NM_001376619.1:c.2807C>T NP_001363548.1:p.Pro936Leu missense NM_001376620.1:c.2732C>T NP_001363549.1:p.Pro911Leu missense NM_001376621.1:c.2807C>T NP_001363550.1:p.Pro936Leu missense NM_001376622.1:c.2936C>T NP_001363551.1:p.Pro979Leu missense NM_001376623.1:c.2936C>T NP_001363552.1:p.Pro979Leu missense NM_001376624.1:c.2867C>T NP_001363553.1:p.Pro956Leu missense NM_001376625.1:c.2867C>T NP_001363554.1:p.Pro956Leu missense NM_001376626.1:c.2792C>T NP_001363555.1:p.Pro931Leu missense NM_001376627.1:c.2663C>T NP_001363556.1:p.Pro888Leu missense NM_001376628.1:c.2867C>T NP_001363557.1:p.Pro956Leu missense NM_001376629.1:c.2867C>T NP_001363558.1:p.Pro956Leu missense NM_001376630.1:c.2867C>T NP_001363559.1:p.Pro956Leu missense NM_001376631.1:c.2909C>T NP_001363560.1:p.Pro970Leu missense NM_001376632.1:c.2840C>T NP_001363561.1:p.Pro947Leu missense NM_001376633.1:c.2996C>T NP_001363562.1:p.Pro999Leu missense NM_001376634.1:c.2996C>T NP_001363563.1:p.Pro999Leu missense NM_001376635.1:c.2663C>T NP_001363564.1:p.Pro888Leu missense NM_001376636.1:c.2867C>T NP_001363565.1:p.Pro956Leu missense NM_001376637.1:c.2867C>T NP_001363566.1:p.Pro956Leu missense NM_001376638.1:c.2867C>T NP_001363567.1:p.Pro956Leu missense NM_001376639.1:c.2867C>T NP_001363568.1:p.Pro956Leu missense NM_001376640.1:c.2807C>T NP_001363569.1:p.Pro936Leu missense NM_001376641.1:c.2807C>T NP_001363570.1:p.Pro936Leu missense NM_001376642.1:c.2867C>T NP_001363571.1:p.Pro956Leu missense NM_001376643.1:c.2867C>T NP_001363572.1:p.Pro956Leu missense NM_001376644.1:c.2603C>T NP_001363573.1:p.Pro868Leu missense NM_001376645.1:c.2807C>T NP_001363574.1:p.Pro936Leu missense NM_001376646.1:c.2663C>T NP_001363575.1:p.Pro888Leu missense NM_001376647.1:c.2603C>T NP_001363576.1:p.Pro868Leu missense NM_001376648.1:c.2792C>T NP_001363577.1:p.Pro931Leu missense NM_001376649.1:c.2780C>T NP_001363578.1:p.Pro927Leu missense NM_001376650.1:c.2705C>T NP_001363579.1:p.Pro902Leu missense NM_001376651.1:c.2807C>T NP_001363580.1:p.Pro936Leu missense NM_001376652.1:c.2807C>T NP_001363581.1:p.Pro936Leu missense NM_001376653.1:c.2807C>T NP_001363582.1:p.Pro936Leu missense NM_001376654.1:c.2663C>T NP_001363583.1:p.Pro888Leu missense NM_001376655.1:c.2867C>T NP_001363584.1:p.Pro956Leu missense NM_001376656.1:c.2807C>T NP_001363585.1:p.Pro936Leu missense NM_001376657.1:c.2732C>T NP_001363586.1:p.Pro911Leu missense NM_001376658.1:c.2705C>T NP_001363587.1:p.Pro902Leu missense NM_001376659.1:c.2663C>T NP_001363588.1:p.Pro888Leu missense NM_001376660.1:c.2603C>T NP_001363589.1:p.Pro868Leu missense NM_001376661.1:c.2807C>T NP_001363590.1:p.Pro936Leu missense NM_001376662.1:c.2525-564C>T intron variant NM_001376663.1:c.2270C>T NP_001363592.1:p.Pro757Leu missense NM_003682.4:c.2996C>T NP_003673.3:p.Pro999Leu missense NM_130470.3:c.2936C>T NP_569826.2:p.Pro979Leu missense NM_130471.3:c.2867C>T NP_569827.2:p.Pro956Leu missense NM_130472.3:c.2807C>T NP_569828.2:p.Pro936Leu missense NM_130473.3:c.2996C>T NP_569829.2:p.Pro999Leu missense NM_130474.3:c.2807C>T NP_569830.2:p.Pro936Leu missense NM_130475.3:c.2996C>T NP_569831.1:p.Pro999Leu missense NM_130476.3:c.2936C>T NP_569832.2:p.Pro979Leu missense NR_164835.1:n.3198C>T non-coding transcript variant NR_164836.1:n.3069C>T non-coding transcript variant NR_164838.1:n.2859C>T non-coding transcript variant NR_164839.1:n.3009C>T non-coding transcript variant NR_164840.1:n.3198C>T non-coding transcript variant NR_164841.1:n.3138C>T non-coding transcript variant NR_164842.1:n.3114C>T non-coding transcript variant NC_000011.10:g.47290046C>T NC_000011.9:g.47311597C>T NG_029462.1:g.25671C>T NG_029462.2:g.25860C>T - Protein change
- P868L, P888L, P945L, P947L, P999L, P757L, P902L, P911L, P936L, P948L, P970L, P1005L, P927L, P931L, P956L, P979L
- Other names
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- Canonical SPDI
- NC_000011.10:47290045:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- 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 | ||
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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. |
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MADD | - | - |
GRCh38 GRCh37 |
227 | 244 |
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. |
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Likely benign (1) |
criteria provided, single submitter
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May 8, 2024 | RCV002960828.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 23, 2022 | RCV003128888.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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- | RCV004527451.1 |
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. |
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Uncertain significance
(Aug 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV003805696.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
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Uncertain significance
(-)
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criteria provided, single submitter
Method: not provided
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Deeah syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University Hospital of Duesseldorf
Accession: SCV005038663.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
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Likely benign
(May 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003680198.3
First in ClinVar: Feb 07, 2023 Last updated: Aug 11, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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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
HelpTitle | Author | Journal | Year | Link |
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Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria. | Pejaver V | American journal of human genetics | 2022 | PMID: 36413997 |
Text-mined citations for this variant ...
HelpRecord last updated Aug 11, 2024
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.