NM_000330.4(RS1):c.416del (p.Gln139fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 13, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000085296.15

Allele description [Variation Report for NM_000330.4(RS1):c.416del (p.Gln139fs)]

NM_000330.4(RS1):c.416del (p.Gln139fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

Xp22.13

Genomic location:

Preferred name:

NM_000330.4(RS1):c.416del (p.Gln139fs)

HGVS:

NC_000023.11:g.18644536del
NG_008475.1:g.223932del
NG_008659.3:g.37913del
NM_000330.4:c.416delMANE SELECT
NM_001037343.2:c.2714-1471del
NM_003159.3:c.2714-1471del
NP_000321.1:p.Gln139Argfs
NP_000321.1:p.Gln139fs
LRG_702t1:c.416del
LRG_702:g.37913del
NC_000023.10:g.18662656del
NM_000330.3:c.416del
NM_000330.3:c.416delA

Protein change:

Q139fs

Links:

dbSNP: rs61752155

NCBI 1000 Genomes Browser:

rs61752155

Molecular consequence:

NM_000330.4:c.416del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001037343.2:c.2714-1471del - intron variant - [Sequence Ontology: SO:0001627]
NM_003159.3:c.2714-1471del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000117433	Retina International	no classification provided	not provided	unknown	not provided
SCV002228700	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 7, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17172462, 9618178, 20238027, 23847049, 29099798, 28492532
SCV005201198	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 13, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000117433

Retina International

no classification provided

not provided

unknown

not provided

SCV002228700

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 7, 2023)

germline

clinical testing

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

SCV005201198

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 13, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

X-linked retinoschisis: an update.

Sikkink SK, Biswas S, Parry NR, Stanga PE, Trump D.

J Med Genet. 2007 Apr;44(4):225-32. Epub 2006 Dec 15. Review.

PubMed [citation]

PMID:: 17172462
PMCID:: PMC2598044

Functional implications of the spectrum of mutations found in 234 cases with X-linked juvenile retinoschisis. The Retinoschisis Consortium.

[No authors listed]

Hum Mol Genet. 1998 Jul;7(7):1185-92.

PubMed [citation]

PMID:: 9618178

See all PubMed Citations (6)

Details of each submission

From Retina International, SCV000117433.1

#	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, SCV002228700.3

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

Description

This sequence change creates a premature translational stop signal (p.Gln139Argfs*10) in the RS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RS1 are known to be pathogenic (PMID: 9618178, 17172462). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with retinoschisis (PMID: 9618178, 20238027, 23847049, 29099798). ClinVar contains an entry for this variant (Variation ID: 98955). For these reasons, this variant has been classified as Pathogenic.

#	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

From GeneDx, SCV005201198.1

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34624300, 35456481, 32037395, 29099798, 9618178, 23847049)

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

Last Updated: Sep 29, 2024

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