Variant classified as Uncertain Significance - Favor Pathogenic. The Gln213X var iant in MYH9 has not been previously reported in individuals with hearing loss a nd was absent from large population studies. This nonsense variant leads to a pr emature termination codon at position 213, which is predicted to lead to a trunc ated or absent protein. The variant occurs in the myosin head domain of the MYH9 protein; however, pathogenic truncating variants have been reported in only exo n 41 (the last exon) of the MYH9 gene, which is located in the tail domain (Pecc i 2013). In addition, in vivo functional analyses in mice support a dominant neg ative mechanism of disease (Matsushita 2004); however these studies may not accu rately model human disease and haploinsufficiency may be a mechanism for pathoge nesis (Balduini 2011). Therefore, the impact of this variant on the protein and its subsequent contribution to the hearing loss cannot be determined without add itional studies. In summary, the clinical significance of this variant cannot be determined at this time.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Uncertain significance
- Review status:
- criteria provided, single submitter
- Submissions:
- 1
- First in ClinVar:
- Feb 2, 2015
- Most recent Submission:
- Feb 2, 2015
- Last evaluated:
- Jul 15, 2014
- Accession:
- VCV000164463.4
- Variation ID:
- 164463
- Description:
- single nucleotide variant
Help
NM_002473.6(MYH9):c.637C>T (p.Gln213Ter)
- Allele ID
- 176405
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 22q12.3
- Genomic location
- 22: 36322497 (GRCh38) GRCh38 UCSC
- 22: 36718542 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_002473.6:c.637C>T MANE Select NP_002464.1:p.Gln213Ter nonsense NC_000022.11:g.36322497G>A NC_000022.10:g.36718542G>A NG_011884.2:g.70522C>T LRG_567:g.70522C>T - Protein change
- Q213*
- Other names
- -
- Canonical SPDI
- NC_000022.11:36322496:G:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- ClinGen: CA177151
- dbSNP: rs727503292
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Uncertain significance | 1 | criteria provided, single submitter | Jul 15, 2014 | RCV000151354.4 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Uncertain significance
(Jul 15, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000199335.4
First in ClinVar: Feb 02, 2015 Last updated: Feb 02, 2015 |
Comment:
Variant classified as Uncertain Significance - Favor Pathogenic. The Gln213X var iant in MYH9 has not been previously reported in individuals with hearing loss a … (more)
Variant classified as Uncertain Significance - Favor Pathogenic. The Gln213X var iant in MYH9 has not been previously reported in individuals with hearing loss a nd was absent from large population studies. This nonsense variant leads to a pr emature termination codon at position 213, which is predicted to lead to a trunc ated or absent protein. The variant occurs in the myosin head domain of the MYH9 protein; however, pathogenic truncating variants have been reported in only exo n 41 (the last exon) of the MYH9 gene, which is located in the tail domain (Pecc i 2013). In addition, in vivo functional analyses in mice support a dominant neg ative mechanism of disease (Matsushita 2004); however these studies may not accu rately model human disease and haploinsufficiency may be a mechanism for pathoge nesis (Balduini 2011). Therefore, the impact of this variant on the protein and its subsequent contribution to the hearing loss cannot be determined without add itional studies. In summary, the clinical significance of this variant cannot be determined at this time. (less)
Number of individuals with the variant: 1
|
Functional evidence
Help| 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 this variant
Help| There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs727503292...
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 Dec 24, 2022