This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 225 of the SGSH protein (p.Phe225Leu). This variant is present in population databases (rs34520362, gnomAD 0.01%). This missense change has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 21204211). ClinVar contains an entry for this variant (Variation ID: 235357). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SGSH protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Conflicting interpretations of pathogenicity
Pathogenic(1); Likely pathogenic(2); Uncertain significance(1)
- Review status:
- criteria provided, conflicting interpretations
- Submissions:
- 4
- First in ClinVar:
- Jun 9, 2016
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Oct 20, 2022
- Accession:
- VCV000235357.7
- Variation ID:
- 235357
- Description:
- single nucleotide variant
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NM_000199.5(SGSH):c.675C>G (p.Phe225Leu)
- Allele ID
- 237044
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 17q25.3
- Genomic location
- 17: 80213874 (GRCh38) GRCh38 UCSC
- 17: 78187673 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000199.5:c.675C>G MANE Select NP_000190.1:p.Phe225Leu missense NM_001352921.3:c.675C>G NP_001339850.1:p.Phe225Leu missense NM_001352922.2:c.675C>G NP_001339851.1:p.Phe225Leu missense NR_148201.2:n.589C>G NC_000017.11:g.80213874G>C NC_000017.10:g.78187673G>C NG_008229.1:g.11527C>G - Protein change
- F225L
- Other names
- -
- Canonical SPDI
- NC_000017.11:80213873:G:C
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- 0.00699 (A)
- Allele frequency
- Trans-Omics for Precision Medicine (TOPMed) 0.00006
- Links
- ClinGen: CA8817846
- dbSNP: rs34520362
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 1 | criteria provided, single submitter | Nov 24, 2015 | RCV000224603.2 | |
| Conflicting interpretations of pathogenicity | 3 | criteria provided, conflicting interpretations | Oct 20, 2022 | RCV000675098.6 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Nov 24, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000280872.2
First in ClinVar: Jun 09, 2016 Last updated: Jun 09, 2016 |
|
|
|
Uncertain significance
(Dec 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis, MPS-III-A
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000800631.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
|
|
|
Likely pathogenic
(Nov 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis, MPS-III-A
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002045099.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
|
|
|
Likely pathogenic
(Oct 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Mucopolysaccharidosis, MPS-III-A
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002285943.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 225 of the SGSH protein (p.Phe225Leu). … (more)
This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 225 of the SGSH protein (p.Phe225Leu). This variant is present in population databases (rs34520362, gnomAD 0.01%). This missense change has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 21204211). ClinVar contains an entry for this variant (Variation ID: 235357). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SGSH protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
|
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| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. | Héron B | American journal of medical genetics. Part A | 2011 | PMID: 21204211 |
Text-mined citations for rs34520362...
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 Feb 07, 2023