NM_001909.5(CTSD):c.299C>T (p.Ser100Phe) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 28, 2018
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:: RCV000187320.2

Allele description [Variation Report for NM_001909.5(CTSD):c.299C>T (p.Ser100Phe)]

NM_001909.5(CTSD):c.299C>T (p.Ser100Phe)

Gene:

CTSD:cathepsin D [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_001909.5(CTSD):c.299C>T (p.Ser100Phe)

Other names:

p.S100F:TCC>TTC

HGVS:

NC_000011.10:g.1759569G>A
NG_008655.1:g.9424C>T
NM_001909.5:c.299C>TMANE SELECT
NP_001900.1:p.Ser100Phe
NC_000011.9:g.1780799G>A
NM_001909.4:c.299C>T

Protein change:

S100F

Links:

dbSNP: rs796052407

NCBI 1000 Genomes Browser:

rs796052407

Molecular consequence:

NM_001909.5:c.299C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000240902	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Feb 28, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000240902

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Feb 28, 2018)

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

Details of each submission

From GeneDx, SCV000240902.11

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

Description

The S100F variant in the CTSD gene has been reported previously in an individual with congenital neuronal lipofuscinosis who was homozygous for the S100F variant (Fritchie et al., 2009). Functional studies of the S100F variant demonstrated a damaging effect with severely reduced cathepsin D enzyme activity (Fritchie et al., 2009). The S100F variant is not observed in large population cohorts (Lek et al., 2016). The S100F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret S100F as a likely pathogenic variant.

#	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: Jan 19, 2025

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