NM_000396.4(CTSK):c.3G>A (p.Met1Ile) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 30, 2023
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:: RCV002530701.3

Allele description [Variation Report for NM_000396.4(CTSK):c.3G>A (p.Met1Ile)]

NM_000396.4(CTSK):c.3G>A (p.Met1Ile)

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.3G>A (p.Met1Ile)

HGVS:

NC_000001.11:g.150806803C>T
NG_011848.1:g.6534G>A
NM_000396.4:c.3G>AMANE SELECT
NP_000387.1:p.Met1Ile
NC_000001.10:g.150779279C>T
NM_000396.3:c.3G>A

Protein change:

M1I

Links:

dbSNP: rs778368118

NCBI 1000 Genomes Browser:

rs778368118

Molecular consequence:

NM_000396.4:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000396.4:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003523508	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 30, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17206399, 24269275, 27092432, 24767306, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523508

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 30, 2023)

germline

clinical testing

PubMed (5)
[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

High bone mineral density in pycnodysostotic patients with a novel mutation in the propeptide of cathepsin K.

Schilling AF, Mülhausen C, Lehmann W, Santer R, Schinke T, Rueger JM, Amling M.

Osteoporos Int. 2007 May;18(5):659-69. Epub 2007 Jan 6.

PubMed [citation]

PMID:: 17206399

Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis.

Pangrazio A, Puddu A, Oppo M, Valentini M, Zammataro L, Vellodi A, Gener B, Llano-Rivas I, Raza J, Atta I, Vezzoni P, Superti-Furga A, Villa A, Sobacchi C.

Bone. 2014 Feb;59:122-6. doi: 10.1016/j.bone.2013.11.014. Epub 2013 Nov 20.

PubMed [citation]

PMID:: 24269275
PMCID:: PMC3885796

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003523508.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects the initiator methionine of the CTSK mRNA. The next in-frame methionine is located at codon 75. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CTSK protein in which other variant(s) (p.Arg46Trp) have been determined to be pathogenic (PMID: 17206399, 24269275, 27092432). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 551777). Disruption of the initiator codon has been observed in individual(s) with pycnodysostosis (PMID: 24767306). This variant is present in population databases (rs778368118, gnomAD 0.003%).

#	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: Sep 29, 2024

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