ClinVar Genomic variation as it relates to human health
NM_002473.6(MYH9):c.3340T>C (p.Ser1114Pro)
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(7)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002473.6(MYH9):c.3340T>C (p.Ser1114Pro)
Variation ID: 164442 Accession: VCV000164442.30
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 22q12.3 22: 36295650 (GRCh38) [ NCBI UCSC ] 22: 36691696 (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 Dec 6, 2016 Apr 15, 2024 Jan 22, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002473.6:c.3340T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002464.1:p.Ser1114Pro missense NM_002473.5:c.3340T>C NC_000022.11:g.36295650A>G NC_000022.10:g.36691696A>G NG_011884.2:g.97369T>C LRG_567:g.97369T>C P35579:p.Ser1114Pro - Protein change
- S1114P
- Other names
- -
- Canonical SPDI
- NC_000022.11:36295649:A:G
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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.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Exome Aggregation Consortium (ExAC) 0.00030
The Genome Aggregation Database (gnomAD), exomes 0.00032
Trans-Omics for Precision Medicine (TOPMed) 0.00043
The Genome Aggregation Database (gnomAD) 0.00044
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
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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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MYH9 | - | - |
GRCh38 GRCh37 |
1339 | 1438 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Nov 2, 2023 | RCV000151335.10 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000268989.6 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000363597.6 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 22, 2024 | RCV000767070.19 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 28, 2019 | RCV000990431.2 | |
Likely benign (1) |
criteria provided, single submitter
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Dec 20, 2022 | RCV003927455.1 |
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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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000199309.4
First in ClinVar: Jan 30, 2015 Last updated: Apr 09, 2018 |
Comment:
p.Ser1114Pro in exon 26 of MYH9: This variant is not expected to have clinical significance because it has been identified in 0.1% (10/10128) of Ashkenazi … (more)
p.Ser1114Pro in exon 26 of MYH9: This variant is not expected to have clinical significance because it has been identified in 0.1% (10/10128) of Ashkenazi Jewi sh chromosomes and in 0.05% (68/126464) of European chromosomes by the Genome Ag gregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200901330) , which is higher than expected based on the estimated prevalence of 1-9/1,000,0 00 of MYH9-related disorder (www.orpha.net, MYH9-related disease, Orpha:182050). (less)
Number of individuals with the variant: 3
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Uncertain significance
(Jul 18, 2023)
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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: SCV000617832.4
First in ClinVar: Dec 19, 2017 Last updated: Jul 29, 2023 |
Comment:
Reported in unrelated patients with MYH9-related disease, however, some of these individuals also harbored an additional disease causing variant on the same allele (in cis) … (more)
Reported in unrelated patients with MYH9-related disease, however, some of these individuals also harbored an additional disease causing variant on the same allele (in cis) (Heath et al., 2001; Saposnik et al., 2014; Westbury et al., 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28368695, 25077172, 30245029, 20588287, 25949529, 29907799, 23804846, 30720677, 11590545) (less)
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Likely benign
(Nov 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004222686.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
Variant summary: MYH9 c.3340T>C (p.Ser1114Pro) results in a non-conservative amino acid change located in the Myosin tail domain (IPR002928) of the encoded protein sequence. Four … (more)
Variant summary: MYH9 c.3340T>C (p.Ser1114Pro) results in a non-conservative amino acid change located in the Myosin tail domain (IPR002928) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 1613794 control chromosomes in the gnomAD v3 database, including 1 homozygote. c.3340T>C has been reported in the literature in individuals affected with Alport syndrome with macrothrombocytopenia, Hereditary chronic kidney disease or Hearing loss (Heath_2001, Sheppard_2018, Popp_2022). These reports do not provide unequivocal conclusions about association of the variant with Macrothrombocytopenia And Granulocyte Inclusions With Or Without Nephritis Or Sensorineural Hearing Loss. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30245029, 11590545, 36100708, 29907799). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=2) and likely benign (n=4). Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Likely benign
(Jan 22, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002364641.3
First in ClinVar: Apr 08, 2022 Last updated: Feb 14, 2024 |
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Likely benign
(Dec 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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MYH9-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004739623.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Feb 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002496739.12
First in ClinVar: Apr 08, 2022 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001141418.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 17
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000438397.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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MYH9-related disorder
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000438396.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (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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Prevalence of hereditary tubulointerstitial kidney diseases in the German Chronic Kidney Disease study. | Popp B | European journal of human genetics : EJHG | 2022 | PMID: 36100708 |
Genomic Landscape and Mutational Signatures of Deafness-Associated Genes. | Azaiez H | American journal of human genetics | 2018 | PMID: 30245029 |
Utility and limitations of exome sequencing as a genetic diagnostic tool for children with hearing loss. | Sheppard S | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29907799 |
Human phenotype ontology annotation and cluster analysis to unravel genetic defects in 707 cases with unexplained bleeding and platelet disorders. | Westbury SK | Genome medicine | 2015 | PMID: 25949529 |
Mutation spectrum and genotype-phenotype correlations in a large French cohort of MYH9-Related Disorders. | Saposnik B | Molecular genetics & genomic medicine | 2014 | PMID: 25077172 |
MYH9-related disease: description of a large Chinese pedigree and a survey of reported mutations. | Zhang S | Acta haematologica | 2014 | PMID: 24643058 |
Advancing genetic testing for deafness with genomic technology. | Shearer AE | Journal of medical genetics | 2013 | PMID: 23804846 |
Glomerular pathology in autosomal dominant MYH9 spectrum disorders: what are the clues telling us about disease mechanism? | Kopp JB | Kidney international | 2010 | PMID: 20588287 |
Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes. | Heath KE | American journal of human genetics | 2001 | PMID: 11590545 |
Text-mined citations for rs200901330 ...
HelpRecord last updated Apr 15, 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.