NM_001909.5(CTSD):c.470C>T (p.Ser157Leu) AND Neuronal ceroid lipofuscinosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 27, 2021
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:: RCV000804177.8

Allele description [Variation Report for NM_001909.5(CTSD):c.470C>T (p.Ser157Leu)]

NM_001909.5(CTSD):c.470C>T (p.Ser157Leu)

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.470C>T (p.Ser157Leu)

HGVS:

NC_000011.10:g.1758970G>A
NG_008655.1:g.10023C>T
NM_001909.5:c.470C>TMANE SELECT
NP_001900.1:p.Ser157Leu
NC_000011.9:g.1780200G>A
NM_001909.4:c.470C>T

Protein change:

S157L

Links:

dbSNP: rs587779409

NCBI 1000 Genomes Browser:

rs587779409

Molecular consequence:

NM_001909.5:c.470C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis
Synonyms:: Ceroid storage disease
Identifiers:: MONDO: MONDO:0016295; MedGen: C0027877; Orphanet: 79263; OMIM: PS256730

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000944073	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 27, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24767253, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000944073

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 27, 2021)

germline

clinical testing

PubMed (2)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders.

Fernández-Marmiesse A, Morey M, Pineda M, Eiris J, Couce ML, Castro-Gago M, Fraga JM, Lacerda L, Gouveia S, Pérez-Poyato MS, Armstrong J, Castiñeiras D, Cocho JA.

Orphanet J Rare Dis. 2014 Apr 25;9:59. doi: 10.1186/1750-1172-9-59.

PubMed [citation]

PMID:: 24767253
PMCID:: PMC4024120

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000944073.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces serine with leucine at codon 157 of the CTSD protein (p.Ser157Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs587779409, ExAC 0.006%). This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 24767253). ClinVar contains an entry for this variant (Variation ID: 100732). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Oct 7, 2023

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