The p.Leu200Arg variant in CHST6 has been reported in at least 17 individuals wi th macular corneal dystrophy who also tested positive for a reduction in keratin sulfate consistent with CHST6 deficiency (14 compound heterozygotes, 1 homozygo te and 2 heterozygotes) (El-Ashry 2002, El-Ashry 2005, Abbruzzese 2004, Klintwor th 2006, Liskova 2008). This variant has been identified in 0.03% (30/115,942) o f chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs28937879). Although it has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency . In summary, this variant meets our criteria to be classified as pathogenic for macular corneal dystrophy in an autosomal recessive manner based upon its biall elic occurrence in affected individuals and functional evidence.
ClinVar Genomic variation as it relates to human health
NM_021615.5(CHST6):c.599T>G (p.Leu200Arg)
Germline
Classification
Help
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.
(11)
Help
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.
Pathogenic
11
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_021615.5(CHST6):c.599T>G (p.Leu200Arg)
Variation ID: 5075 Accession: VCV000005075.45
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16q23.1 16: 75479230 (GRCh38) [ NCBI UCSC ] 16: 75513128 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 1, 2015 Nov 17, 2024 Sep 10, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_021615.5:c.599T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_067628.1:p.Leu200Arg missense NC_000016.10:g.75479230A>C NC_000016.9:g.75513128A>C NG_016442.2:g.21212T>G LRG_1252:g.21212T>G LRG_1252t1:c.599T>G LRG_1252p1:p.Leu200Arg Q9GZX3:p.Leu200Arg - Protein change
- L200R
- Other names
- -
- Canonical SPDI
- NC_000016.10:75479229:A:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00019
The Genome Aggregation Database (gnomAD) 0.00022
The Genome Aggregation Database (gnomAD), exomes 0.00022
Exome Aggregation Consortium (ExAC) 0.00026
- 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. |
|||
| CHST6 | - | - |
GRCh38 GRCh37 |
302 | 353 | |
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. |
|---|---|---|---|---|
| Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
|
Sep 10, 2024 | RCV000005379.25 | |
| Pathogenic (1) |
no assertion criteria provided
|
Mar 1, 2004 | RCV000005380.6 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Sep 1, 2019 | RCV001091757.22 | |
|
CHST6-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Aug 27, 2024 | RCV004757947.1 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jun 28, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Macular corneal dystrophy
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966880.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
The p.Leu200Arg variant in CHST6 has been reported in at least 17 individuals wi th macular corneal dystrophy who also tested positive for a reduction … (more)
The p.Leu200Arg variant in CHST6 has been reported in at least 17 individuals wi th macular corneal dystrophy who also tested positive for a reduction in keratin sulfate consistent with CHST6 deficiency (14 compound heterozygotes, 1 homozygo te and 2 heterozygotes) (El-Ashry 2002, El-Ashry 2005, Abbruzzese 2004, Klintwor th 2006, Liskova 2008). This variant has been identified in 0.03% (30/115,942) o f chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs28937879). Although it has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency . In summary, this variant meets our criteria to be classified as pathogenic for macular corneal dystrophy in an autosomal recessive manner based upon its biall elic occurrence in affected individuals and functional evidence. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Oct 13, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Macular corneal dystrophy
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV001981637.3
First in ClinVar: Oct 25, 2021 Last updated: Dec 17, 2022 |
|
|
|
Pathogenic
(Nov 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Macular corneal dystrophy
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002196898.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 200 of the CHST6 protein (p.Leu200Arg). … (more)
This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 200 of the CHST6 protein (p.Leu200Arg). This variant is present in population databases (rs28937879, gnomAD 0.05%). This missense change has been observed in individuals with macular corneal dystrophy (PMID: 11818380, 16568029, 32472422). It has also been observed to segregate with disease in related individuals. This variant is also known as 1291T>G. ClinVar contains an entry for this variant (Variation ID: 5075). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jan 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Macular corneal dystrophy
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000915733.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The CHST6 c.599T>G (p.Leu200Arg) missense variant has been reported in at least seven studies in which it is identified in a total of 37 individuals … (more)
The CHST6 c.599T>G (p.Leu200Arg) missense variant has been reported in at least seven studies in which it is identified in a total of 37 individuals with macular corneal dystrophy (MCD) type I or II from 31 families, including in seven in a homozygous state (two of whom are related); 19 in a compound heterozygous state (two of whom are related); and 11 in a heterozygous state (two of whom are related) (El-Ashry et al. 2002; Aldave et al. 2004; Klintworth et al. 2006; Gruenauer-Kloevekorn et al. 2008; Liskova et al. 2008; Dudakova et al. 2014; Nowinska et al. 2014). The p.Leu200Arg variant was detected in a heterozygous state in one of 694 control chromosomes and is reported at a frequency of 0.000471 in the European (non-Finnish) population of the Genome Aggregation Database. The Leu200 residue is noted to be highly conserved. Based on the collective evidence, the p.Leu200Arg variant is classified as pathogenic for macular corneal dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
|
Pathogenic
(May 09, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Macular corneal dystrophy
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002581472.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS4, PM3_STR, PM2_SUP, PP1, PP3
|
Number of individuals with the variant: 1
Sex: male
|
|
|
Pathogenic
(Feb 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Macular corneal dystrophy
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002811692.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Sep 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247963.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Sep 10, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Macular corneal dystrophy
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005395075.1
First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024 |
Comment:
Variant summary: CHST6 c.599T>G (p.Leu200Arg) results in a non-conservative amino acid change located in the Sulfotransferase domain (IPR000863) of the encoded protein sequence. Five of … (more)
Variant summary: CHST6 c.599T>G (p.Leu200Arg) results in a non-conservative amino acid change located in the Sulfotransferase domain (IPR000863) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 244732 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CHST6 causing Macular Corneal Dystrophy (0.00022 vs 0.0013), allowing no conclusion about variant significance. c.599T>G has been reported in the literature as a biallelic genotype in multiple individuals affected with Macular Corneal Dystrophy (example, El Ashry_2002, Safari_2020, Souzeau_2022). These data indicate that the variant is very likely to be associated with disease. 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: 11818380, 32472422, 35985662). ClinVar contains an entry for this variant (Variation ID: 5075). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Mar 01, 2004)
|
no assertion criteria provided
Method: literature only
|
MACULAR CORNEAL DYSTROPHY, TYPE I
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000025559.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2015 |
Comment on evidence:
In affected members of 3 families with type I macular corneal dystrophy (MCD; 217800), Aldave et al. (2004) identified compound heterozygosity for a 1291T-G transversion … (more)
In affected members of 3 families with type I macular corneal dystrophy (MCD; 217800), Aldave et al. (2004) identified compound heterozygosity for a 1291T-G transversion in the CHST6 gene, resulting in a leu200-to-arg (L200R) substitution, and another mutation: a 996T-G transversion, resulting in a cys102-to-gly mutation (C102G; 605294.0006); a 1021A-G transition, resulting in a tyr110-to-cys mutation (Y110C; 605294.0007); or a 1519T-C transition, resulting in a leu276-to-pro mutation (L276P; 605294.0008). In affected members of 2 families with type II macular corneal dystrophy, Aldave et al. (2004) identified compound heterozygosity for the L200R mutation and another mutation: a 969C-A transversion, resulting in an arg93-to-ser mutation (R93S; 605294.0009), or an unidentified mutation. Haplotype analysis using microsatellite markers flanking the CHST6 gene did not reveal a common founder effect for the L200R mutation, suggesting its position as a mutation hotspot. (less)
|
|
|
Pathogenic
(Mar 01, 2004)
|
no assertion criteria provided
Method: literature only
|
MACULAR CORNEAL DYSTROPHY, TYPE II
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000025560.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2015 |
Comment on evidence:
In affected members of 3 families with type I macular corneal dystrophy (MCD; 217800), Aldave et al. (2004) identified compound heterozygosity for a 1291T-G transversion … (more)
In affected members of 3 families with type I macular corneal dystrophy (MCD; 217800), Aldave et al. (2004) identified compound heterozygosity for a 1291T-G transversion in the CHST6 gene, resulting in a leu200-to-arg (L200R) substitution, and another mutation: a 996T-G transversion, resulting in a cys102-to-gly mutation (C102G; 605294.0006); a 1021A-G transition, resulting in a tyr110-to-cys mutation (Y110C; 605294.0007); or a 1519T-C transition, resulting in a leu276-to-pro mutation (L276P; 605294.0008). In affected members of 2 families with type II macular corneal dystrophy, Aldave et al. (2004) identified compound heterozygosity for the L200R mutation and another mutation: a 969C-A transversion, resulting in an arg93-to-ser mutation (R93S; 605294.0009), or an unidentified mutation. Haplotype analysis using microsatellite markers flanking the CHST6 gene did not reveal a common founder effect for the L200R mutation, suggesting its position as a mutation hotspot. (less)
|
|
|
Pathogenic
(Aug 27, 2024)
|
no assertion criteria provided
Method: clinical testing
|
CHST6-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV005360800.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The CHST6 c.599T>G variant is predicted to result in the amino acid substitution p.Leu200Arg. This variant has been reported along with one or more other … (more)
The CHST6 c.599T>G variant is predicted to result in the amino acid substitution p.Leu200Arg. This variant has been reported along with one or more other CHST6 variants in multiple individuals with macular corneal dystrophy (El-Ashry et al. 2002. PubMed ID: 11818380; Klintworth et al. 2006. PubMed ID: 16568029; Weiss et al. 2008. PubMed ID: 19337156; Safari et al. 2020. PubMed ID: 32472422), and is considered a mutation hot-spot (Aldave et al. 2004. PubMed ID: 15013869). This variant is reported in 0.047% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. (less)
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 200 of the CHST6 protein (p.Leu200Arg). This variant is present in population databases (rs28937879, gnomAD 0.05%). This missense change has been observed in individuals with macular corneal dystrophy (PMID: 11818380, 16568029, 32472422). It has also been observed to segregate with disease in related individuals. This variant is also known as 1291T>G. ClinVar contains an entry for this variant (Variation ID: 5075). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Comment:
The CHST6 c.599T>G (p.Leu200Arg) missense variant has been reported in at least seven studies in which it is identified in a total of 37 individuals with macular corneal dystrophy (MCD) type I or II from 31 families, including in seven in a homozygous state (two of whom are related); 19 in a compound heterozygous state (two of whom are related); and 11 in a heterozygous state (two of whom are related) (El-Ashry et al. 2002; Aldave et al. 2004; Klintworth et al. 2006; Gruenauer-Kloevekorn et al. 2008; Liskova et al. 2008; Dudakova et al. 2014; Nowinska et al. 2014). The p.Leu200Arg variant was detected in a heterozygous state in one of 694 control chromosomes and is reported at a frequency of 0.000471 in the European (non-Finnish) population of the Genome Aggregation Database. The Leu200 residue is noted to be highly conserved. Based on the collective evidence, the p.Leu200Arg variant is classified as pathogenic for macular corneal dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Comment:
Variant summary: CHST6 c.599T>G (p.Leu200Arg) results in a non-conservative amino acid change located in the Sulfotransferase domain (IPR000863) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 244732 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CHST6 causing Macular Corneal Dystrophy (0.00022 vs 0.0013), allowing no conclusion about variant significance. c.599T>G has been reported in the literature as a biallelic genotype in multiple individuals affected with Macular Corneal Dystrophy (example, El Ashry_2002, Safari_2020, Souzeau_2022). These data indicate that the variant is very likely to be associated with disease. 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: 11818380, 32472422, 35985662). ClinVar contains an entry for this variant (Variation ID: 5075). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
The CHST6 c.599T>G variant is predicted to result in the amino acid substitution p.Leu200Arg. This variant has been reported along with one or more other CHST6 variants in multiple individuals with macular corneal dystrophy (El-Ashry et al. 2002. PubMed ID: 11818380; Klintworth et al. 2006. PubMed ID: 16568029; Weiss et al. 2008. PubMed ID: 19337156; Safari et al. 2020. PubMed ID: 32472422), and is considered a mutation hot-spot (Aldave et al. 2004. PubMed ID: 15013869). This variant is reported in 0.047% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.
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. |
Comment:
The p.Leu200Arg variant in CHST6 has been reported in at least 17 individuals wi th macular corneal dystrophy who also tested positive for a reduction in keratin sulfate consistent with CHST6 deficiency (14 compound heterozygotes, 1 homozygo te and 2 heterozygotes) (El-Ashry 2002, El-Ashry 2005, Abbruzzese 2004, Klintwor th 2006, Liskova 2008). This variant has been identified in 0.03% (30/115,942) o f chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs28937879). Although it has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency . In summary, this variant meets our criteria to be classified as pathogenic for macular corneal dystrophy in an autosomal recessive manner based upon its biall elic occurrence in affected individuals and functional evidence.
Comment:
This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 200 of the CHST6 protein (p.Leu200Arg). This variant is present in population databases (rs28937879, gnomAD 0.05%). This missense change has been observed in individuals with macular corneal dystrophy (PMID: 11818380, 16568029, 32472422). It has also been observed to segregate with disease in related individuals. This variant is also known as 1291T>G. ClinVar contains an entry for this variant (Variation ID: 5075). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Comment:
The CHST6 c.599T>G (p.Leu200Arg) missense variant has been reported in at least seven studies in which it is identified in a total of 37 individuals with macular corneal dystrophy (MCD) type I or II from 31 families, including in seven in a homozygous state (two of whom are related); 19 in a compound heterozygous state (two of whom are related); and 11 in a heterozygous state (two of whom are related) (El-Ashry et al. 2002; Aldave et al. 2004; Klintworth et al. 2006; Gruenauer-Kloevekorn et al. 2008; Liskova et al. 2008; Dudakova et al. 2014; Nowinska et al. 2014). The p.Leu200Arg variant was detected in a heterozygous state in one of 694 control chromosomes and is reported at a frequency of 0.000471 in the European (non-Finnish) population of the Genome Aggregation Database. The Leu200 residue is noted to be highly conserved. Based on the collective evidence, the p.Leu200Arg variant is classified as pathogenic for macular corneal dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Comment:
Variant summary: CHST6 c.599T>G (p.Leu200Arg) results in a non-conservative amino acid change located in the Sulfotransferase domain (IPR000863) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 244732 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CHST6 causing Macular Corneal Dystrophy (0.00022 vs 0.0013), allowing no conclusion about variant significance. c.599T>G has been reported in the literature as a biallelic genotype in multiple individuals affected with Macular Corneal Dystrophy (example, El Ashry_2002, Safari_2020, Souzeau_2022). These data indicate that the variant is very likely to be associated with disease. 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: 11818380, 32472422, 35985662). ClinVar contains an entry for this variant (Variation ID: 5075). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
The CHST6 c.599T>G variant is predicted to result in the amino acid substitution p.Leu200Arg. This variant has been reported along with one or more other CHST6 variants in multiple individuals with macular corneal dystrophy (El-Ashry et al. 2002. PubMed ID: 11818380; Klintworth et al. 2006. PubMed ID: 16568029; Weiss et al. 2008. PubMed ID: 19337156; Safari et al. 2020. PubMed ID: 32472422), and is considered a mutation hot-spot (Aldave et al. 2004. PubMed ID: 15013869). This variant is reported in 0.047% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Diagnostic yield of candidate genes in an Australian corneal dystrophy cohort. | Souzeau E | Molecular genetics & genomic medicine | 2022 | PMID: 35985662 |
| CHST6 mutations identified in Iranian MCD patients and CHST6 mutations reported worldwide identify targets for gene editing approaches including the CRISPR/Cas system. | Safari I | International ophthalmology | 2020 | PMID: 32472422 |
| Macular corneal dystrophy and associated corneal thinning. | Dudakova L | Eye (London, England) | 2014 | PMID: 25081284 |
| Phenotype and genotype analysis in patients with macular corneal dystrophy. | Nowinska AK | The British journal of ophthalmology | 2014 | PMID: 24926691 |
| Macular corneal dystrophy: mutational spectrum in German patients, novel mutations and therapeutic options. | Gruenauer-Kloevekorn C | Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie | 2008 | PMID: 18500531 |
| Sequencing of the CHST6 gene in Czech macular corneal dystrophy patients supports the evidence of a founder mutation. | Liskova P | The British journal of ophthalmology | 2008 | PMID: 17962390 |
| CHST6 mutations in North American subjects with macular corneal dystrophy: a comprehensive molecular genetic review. | Klintworth GK | Molecular vision | 2006 | PMID: 16568029 |
| Novel CHST6 nonsense and missense mutations responsible for macular corneal dystrophy. | El-Ashry MF | American journal of ophthalmology | 2005 | PMID: 15652851 |
| Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy. | Aldave AJ | American journal of ophthalmology | 2004 | PMID: 15013869 |
| Novel mutations in the CHST6 gene causing macular corneal dystrophy. | Abbruzzese C | Clinical genetics | 2004 | PMID: 14984470 |
| Truncating mutations in the carbohydrate sulfotransferase 6 gene (CHST6) result in macular corneal dystrophy. | Niel F | Investigative ophthalmology & visual science | 2003 | PMID: 12824236 |
| Identification of novel mutations in the carbohydrate sulfotransferase gene (CHST6) causing macular corneal dystrophy. | El-Ashry MF | Investigative ophthalmology & visual science | 2002 | PMID: 11818380 |
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Text-mined citations for rs28937879 ...
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 Nov 19, 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.