NM_000330.4(RS1):c.329G>A (p.Cys110Tyr) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 3, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000085278.18

Allele description [Variation Report for NM_000330.4(RS1):c.329G>A (p.Cys110Tyr)]

NM_000330.4(RS1):c.329G>A (p.Cys110Tyr)

Genes:

CDKL5:cyclin dependent kinase like 5 [Gene - OMIM - HGNC]
RS1:retinoschisin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp22.13

Genomic location:

Preferred name:

NM_000330.4(RS1):c.329G>A (p.Cys110Tyr)

HGVS:

NC_000023.11:g.18644623C>T
NG_008475.1:g.224019C>T
NG_008659.3:g.37826G>A
NM_000330.4:c.329G>AMANE SELECT
NM_001037343.2:c.2714-1384C>T
NM_003159.3:c.2714-1384C>T
NP_000321.1:p.Cys110Tyr
NP_000321.1:p.Cys110Tyr
LRG_702t1:c.329G>A
LRG_702:g.37826G>A
LRG_702p1:p.Cys110Tyr
NC_000023.10:g.18662743C>T
NM_000330.3:c.329G>A
O15537:p.Cys110Tyr

Protein change:

C110Y

Links:

UniProtKB: O15537#VAR_008222; dbSNP: rs61752075

NCBI 1000 Genomes Browser:

rs61752075

Molecular consequence:

NM_001037343.2:c.2714-1384C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_003159.3:c.2714-1384C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000330.4:c.329G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Timoniella imbutiforme isolate YK181 small subunit ribosomal RNA gene, partial s...
Timoniella imbutiforme isolate YK181 small subunit ribosomal RNA gene, partial sequence; internal transcribed spacer 1, complete sequence; and 5.8S ribosomal RNA gene, partial sequence
gi|1216631918|gb|MF491837.1|

Nucleotide
Timoniella sp. MD-2021 isolate ITS-46 internal transcribed spacer 1, partial seq...
Timoniella sp. MD-2021 isolate ITS-46 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene and internal transcribed spacer 2, complete sequence; and large subunit ribosomal RNA gene, partial sequence
gi|2070425463|gb|MZ595828.1|

Nucleotide
Timoniella cf. balthica AB-2017 isolate YK285 large subunit ribosomal RNA gene, ...
Timoniella cf. balthica AB-2017 isolate YK285 large subunit ribosomal RNA gene, partial sequence
gi|1216632239|gb|MF491858.1|

Nucleotide
RecName: Full=Pentatricopeptide repeat-containing protein 1, mitochondrial
RecName: Full=Pentatricopeptide repeat-containing protein 1, mitochondrial
gi|341941747|sp|Q8C2E4.2|PTCD1_MOUS

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000117415	Retina International	no classification provided	not provided	unknown	not provided
SCV001215257	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16361673, 19849666, 9618178, 23453514, 30551202, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000117415

Retina International

no classification provided

not provided

unknown

not provided

SCV001215257

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2022)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular pathology of X linked retinoschisis: mutations interfere with retinoschisin secretion and oligomerisation.

Wang T, Zhou A, Waters CT, O'Connor E, Read RJ, Trump D.

Br J Ophthalmol. 2006 Jan;90(1):81-6.

PubMed [citation]

PMID:: 16361673
PMCID:: PMC1856892

Wild-type and missense mutants of retinoschisin co-assemble resulting in either intracellular retention or incorrect assembly of the functionally active octamer.

Gleghorn LJ, Trump D, Bulleid NJ.

Biochem J. 2009 Dec 14;425(1):275-83. doi: 10.1042/BJ20091179.

PubMed [citation]

PMID:: 19849666

See all PubMed Citations (6)

Details of each submission

From Retina International, SCV000117415.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001215257.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RS1 function (PMID: 16361673, 19849666). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 98938). This missense change has been observed in individuals with X-linked retinoschisis (PMID: 9618178, 23453514, 30551202). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 110 of the RS1 protein (p.Cys110Tyr).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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