ClinVar Genomic variation as it relates to human health
NM_001376571.1(MADD):c.1037T>C (p.Leu346Pro)
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.
Likely pathogenic(2); Uncertain significance(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.1037T>C (p.Leu346Pro)
Variation ID: 806672 Accession: VCV000806672.30
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p11.2 11: 47276805 (GRCh38) [ NCBI UCSC ] 11: 47298356 (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 3, 2020 Oct 20, 2024 Aug 5, 2021 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001376571.1:c.1037T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001363500.1:p.Leu346Pro missense NM_001135943.2:c.1037T>C NP_001129415.1:p.Leu346Pro missense NM_001135944.2:c.1037T>C NP_001129416.1:p.Leu346Pro missense NM_001376572.1:c.1037T>C NP_001363501.1:p.Leu346Pro missense NM_001376573.1:c.1037T>C NP_001363502.1:p.Leu346Pro missense NM_001376574.1:c.1037T>C NP_001363503.1:p.Leu346Pro missense NM_001376575.1:c.1037T>C NP_001363504.1:p.Leu346Pro missense NM_001376576.1:c.1037T>C NP_001363505.1:p.Leu346Pro missense NM_001376577.1:c.1037T>C NP_001363506.1:p.Leu346Pro missense NM_001376578.1:c.1037T>C NP_001363507.1:p.Leu346Pro missense NM_001376579.1:c.1037T>C NP_001363508.1:p.Leu346Pro missense NM_001376580.1:c.1037T>C NP_001363509.1:p.Leu346Pro missense NM_001376581.1:c.1037T>C NP_001363510.1:p.Leu346Pro missense NM_001376582.1:c.1037T>C NP_001363511.1:p.Leu346Pro missense NM_001376583.1:c.1037T>C NP_001363512.1:p.Leu346Pro missense NM_001376584.1:c.1037T>C NP_001363513.1:p.Leu346Pro missense NM_001376585.1:c.1037T>C NP_001363514.1:p.Leu346Pro missense NM_001376586.1:c.1037T>C NP_001363515.1:p.Leu346Pro missense NM_001376593.1:c.1037T>C NP_001363522.1:p.Leu346Pro missense NM_001376594.1:c.1037T>C NP_001363523.1:p.Leu346Pro missense NM_001376595.1:c.1037T>C NP_001363524.1:p.Leu346Pro missense NM_001376596.1:c.1037T>C NP_001363525.1:p.Leu346Pro missense NM_001376597.1:c.1037T>C NP_001363526.1:p.Leu346Pro missense NM_001376598.1:c.1037T>C NP_001363527.1:p.Leu346Pro missense NM_001376599.1:c.1037T>C NP_001363528.1:p.Leu346Pro missense NM_001376600.1:c.1037T>C NP_001363529.1:p.Leu346Pro missense NM_001376601.1:c.1037T>C NP_001363530.1:p.Leu346Pro missense NM_001376602.1:c.1037T>C NP_001363531.1:p.Leu346Pro missense NM_001376603.1:c.1037T>C NP_001363532.1:p.Leu346Pro missense NM_001376604.1:c.1037T>C NP_001363533.1:p.Leu346Pro missense NM_001376605.1:c.1037T>C NP_001363534.1:p.Leu346Pro missense NM_001376606.1:c.1037T>C NP_001363535.1:p.Leu346Pro missense NM_001376607.1:c.1037T>C NP_001363536.1:p.Leu346Pro missense NM_001376608.1:c.1037T>C NP_001363537.1:p.Leu346Pro missense NM_001376609.1:c.1037T>C NP_001363538.1:p.Leu346Pro missense NM_001376610.1:c.1037T>C NP_001363539.1:p.Leu346Pro missense NM_001376611.1:c.1037T>C NP_001363540.1:p.Leu346Pro missense NM_001376612.1:c.1037T>C NP_001363541.1:p.Leu346Pro missense NM_001376613.1:c.1037T>C NP_001363542.1:p.Leu346Pro missense NM_001376614.1:c.1037T>C NP_001363543.1:p.Leu346Pro missense NM_001376615.1:c.1037T>C NP_001363544.1:p.Leu346Pro missense NM_001376616.1:c.1037T>C NP_001363545.1:p.Leu346Pro missense NM_001376617.1:c.1037T>C NP_001363546.1:p.Leu346Pro missense NM_001376618.1:c.1037T>C NP_001363547.1:p.Leu346Pro missense NM_001376619.1:c.1037T>C NP_001363548.1:p.Leu346Pro missense NM_001376620.1:c.833T>C NP_001363549.1:p.Leu278Pro missense NM_001376621.1:c.1037T>C NP_001363550.1:p.Leu346Pro missense NM_001376622.1:c.1037T>C NP_001363551.1:p.Leu346Pro missense NM_001376623.1:c.1037T>C NP_001363552.1:p.Leu346Pro missense NM_001376624.1:c.1037T>C NP_001363553.1:p.Leu346Pro missense NM_001376625.1:c.1037T>C NP_001363554.1:p.Leu346Pro missense NM_001376626.1:c.833T>C NP_001363555.1:p.Leu278Pro missense NM_001376627.1:c.833T>C NP_001363556.1:p.Leu278Pro missense NM_001376628.1:c.1037T>C NP_001363557.1:p.Leu346Pro missense NM_001376629.1:c.1037T>C NP_001363558.1:p.Leu346Pro missense NM_001376630.1:c.1037T>C NP_001363559.1:p.Leu346Pro missense NM_001376631.1:c.1037T>C NP_001363560.1:p.Leu346Pro missense NM_001376632.1:c.1037T>C NP_001363561.1:p.Leu346Pro missense NM_001376633.1:c.1037T>C NP_001363562.1:p.Leu346Pro missense NM_001376634.1:c.1037T>C NP_001363563.1:p.Leu346Pro missense NM_001376635.1:c.833T>C NP_001363564.1:p.Leu278Pro missense NM_001376636.1:c.1037T>C NP_001363565.1:p.Leu346Pro missense NM_001376637.1:c.1037T>C NP_001363566.1:p.Leu346Pro missense NM_001376638.1:c.1037T>C NP_001363567.1:p.Leu346Pro missense NM_001376639.1:c.1037T>C NP_001363568.1:p.Leu346Pro missense NM_001376640.1:c.1037T>C NP_001363569.1:p.Leu346Pro missense NM_001376641.1:c.1037T>C NP_001363570.1:p.Leu346Pro missense NM_001376642.1:c.1037T>C NP_001363571.1:p.Leu346Pro missense NM_001376643.1:c.1037T>C NP_001363572.1:p.Leu346Pro missense NM_001376644.1:c.833T>C NP_001363573.1:p.Leu278Pro missense NM_001376645.1:c.1037T>C NP_001363574.1:p.Leu346Pro missense NM_001376646.1:c.833T>C NP_001363575.1:p.Leu278Pro missense NM_001376647.1:c.833T>C NP_001363576.1:p.Leu278Pro missense NM_001376648.1:c.833T>C NP_001363577.1:p.Leu278Pro missense NM_001376649.1:c.1037T>C NP_001363578.1:p.Leu346Pro missense NM_001376650.1:c.1037T>C NP_001363579.1:p.Leu346Pro missense NM_001376651.1:c.1037T>C NP_001363580.1:p.Leu346Pro missense NM_001376652.1:c.1037T>C NP_001363581.1:p.Leu346Pro missense NM_001376653.1:c.1037T>C NP_001363582.1:p.Leu346Pro missense NM_001376654.1:c.833T>C NP_001363583.1:p.Leu278Pro missense NM_001376655.1:c.1037T>C NP_001363584.1:p.Leu346Pro missense NM_001376656.1:c.1037T>C NP_001363585.1:p.Leu346Pro missense NM_001376657.1:c.833T>C NP_001363586.1:p.Leu278Pro missense NM_001376658.1:c.1037T>C NP_001363587.1:p.Leu346Pro missense NM_001376659.1:c.833T>C NP_001363588.1:p.Leu278Pro missense NM_001376660.1:c.833T>C NP_001363589.1:p.Leu278Pro missense NM_001376661.1:c.1037T>C NP_001363590.1:p.Leu346Pro missense NM_001376662.1:c.1037T>C NP_001363591.1:p.Leu346Pro missense NM_001376663.1:c.371T>C NP_001363592.1:p.Leu124Pro missense NM_003682.4:c.1037T>C NP_003673.3:p.Leu346Pro missense NM_130470.3:c.1037T>C NP_569826.2:p.Leu346Pro missense NM_130471.3:c.1037T>C NP_569827.2:p.Leu346Pro missense NM_130472.3:c.1037T>C NP_569828.2:p.Leu346Pro missense NM_130473.3:c.1037T>C NP_569829.2:p.Leu346Pro missense NM_130474.3:c.1037T>C NP_569830.2:p.Leu346Pro missense NM_130475.3:c.1037T>C NP_569831.1:p.Leu346Pro missense NM_130476.3:c.1037T>C NP_569832.2:p.Leu346Pro missense NR_164835.1:n.1239T>C non-coding transcript variant NR_164836.1:n.1239T>C non-coding transcript variant NR_164837.1:n.1239T>C non-coding transcript variant NR_164838.1:n.1089T>C non-coding transcript variant NR_164839.1:n.1239T>C non-coding transcript variant NR_164840.1:n.1239T>C non-coding transcript variant NR_164841.1:n.1239T>C non-coding transcript variant NR_164842.1:n.1239T>C non-coding transcript variant NC_000011.10:g.47276805T>C NC_000011.9:g.47298356T>C NG_029462.1:g.12430T>C - Protein change
- L346P, L278P, L124P
- Other names
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- Canonical SPDI
- NC_000011.10:47276804:T:C
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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 | ||
|---|---|---|---|---|---|---|
| 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 |
243 | 260 | |
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
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Jan 1, 2019 | RCV000994628.22 | |
| Likely pathogenic (1) |
criteria provided, single submitter
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Aug 1, 2020 | RCV001784525.2 | |
| Likely pathogenic (1) |
criteria provided, single submitter
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Aug 5, 2021 | RCV002290509.3 |
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. |
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Likely pathogenic
(Aug 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002026212.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Likely pathogenic
(Aug 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Deeah syndrome
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002579245.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS4, PM1, PM2_SUP, PM3_SUP, PP3
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Number of individuals with the variant: 1
Sex: male
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Uncertain significance
(Jan 01, 2019)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001148265.27
First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 4
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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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Biallelic MADD variants cause a phenotypic spectrum ranging from developmental delay to a multisystem disorder. | Schneeberger PE | Brain : a journal of neurology | 2020 | PMID: 32761064 |
Text-mined citations for rs1591767154 ...
HelpRecord last updated Oct 20, 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.