NM_000396.4(CTSK):c.926T>C (p.Leu309Pro) AND Pyknodysostosis

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Oct 17, 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:: RCV000008937.10

Allele description [Variation Report for NM_000396.4(CTSK):c.926T>C (p.Leu309Pro)]

NM_000396.4(CTSK):c.926T>C (p.Leu309Pro)

Gene:

CTSK:cathepsin K [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.3

Genomic location:

Preferred name:

NM_000396.4(CTSK):c.926T>C (p.Leu309Pro)

HGVS:

NC_000001.11:g.150796863A>G
NG_011848.1:g.16474T>C
NM_000396.4:c.926T>CMANE SELECT
NP_000387.1:p.Leu309Pro
NC_000001.10:g.150769339A>G
NM_000396.3:c.926T>C
P43235:p.Leu309Pro

Protein change:

L309P; LEU309PRO

Links:

UniProtKB: P43235#VAR_006726; OMIM: 601105.0007; dbSNP: rs29001685

NCBI 1000 Genomes Browser:

rs29001685

Molecular consequence:

NM_000396.4:c.926T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Pyknodysostosis
Synonyms:: Pycnodysostosis
Identifiers:: MONDO: MONDO:0009940; MedGen: C0238402; Orphanet: 763; OMIM: 265800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029147	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000220528	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Jul 19, 2014)	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 21099701, 10878663 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV004049711	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004215237	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 17, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Familial pycnodysostosis: identification of a novel mutation in the CTSK gene (cathepsin K).

Toral-López J, Gonzalez-Huerta LM, Sosa B, Orozco S, González HP, Cuevas-Covarrubias SA.

J Investig Med. 2011 Feb;59(2):277-80. doi: 10.231/JIM.0b013e318202a9db.

PubMed [citation]

PMID:: 21099701

Cathepsin K gene mutations and 1q21 haplotypes in at patients with pycnodysostosis in an outbred population.

Haagerup A, Hertz JM, Christensen MF, Binderup H, Kruse TA.

Eur J Hum Genet. 2000 Jun;8(6):431-6.

PubMed [citation]

PMID:: 10878663

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000029147.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

Of 5 ostensibly unrelated pycnodysostosis (265800) families in Denmark, Haagerup et al. (2000) found that affected members in 3 families were homozygous for a 926T-C transition in exon 8 of the CTSK gene, resulting in a leu309-to-pro (L309P) mutation, whereas affected members in the 2 other families were compound heterozygotes with this mutation and, in each case, a second novel mutation. A very rare haplotype was found in 7 of 8 chromosomes carrying the 926T-C mutation underlying the L309P amino acid substitution.

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

From Counsyl, SCV000220528.2

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

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

From Genome-Nilou Lab, SCV004049711.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004215237.1

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

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

Last Updated: Sep 29, 2024

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