NM_002340.6(LSS):c.1810C>T (p.Arg604Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 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:: RCV003838066.2

Allele description [Variation Report for NM_002340.6(LSS):c.1810C>T (p.Arg604Ter)]

NM_002340.6(LSS):c.1810C>T (p.Arg604Ter)

Gene:

LSS:lanosterol synthase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_002340.6(LSS):c.1810C>T (p.Arg604Ter)

HGVS:

NC_000021.9:g.46195683G>A
NG_011510.1:g.38142C>T
NM_001001438.3:c.1810C>T
NM_001145436.2:c.1777C>T
NM_001145437.2:c.1570C>T
NM_002340.6:c.1810C>TMANE SELECT
NP_001001438.1:p.Arg604Ter
NP_001138908.1:p.Arg593Ter
NP_001138909.1:p.Arg524Ter
NP_002331.3:p.Arg604Ter
NC_000021.8:g.47615597G>A

Protein change:

R524*

Molecular consequence:

NM_001001438.3:c.1810C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001145436.2:c.1777C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001145437.2:c.1570C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_002340.6:c.1810C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004631058	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30723320, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004631058

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 2023)

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

Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome.

Besnard T, Sloboda N, Goldenberg A, Küry S, Cogné B, Breheret F, Trochu E, Conrad S, Vincent M, Deb W, Balguerie X, Barbarot S, Baujat G, Ben-Omran T, Bursztejn AC, Carmignac V, Datta AN, Delignières A, Faivre L, Gardie B, Guéant JL, Kuentz P, et al.

Genet Med. 2019 Sep;21(9):2025-2035. doi: 10.1038/s41436-019-0445-x. Epub 2019 Feb 6.

PubMed [citation]

PMID:: 30723320

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004631058.1

#	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 creates a premature translational stop signal (p.Arg604*) in the LSS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LSS are known to be pathogenic (PMID: 30723320). This variant is present in population databases (rs369619415, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with LSS-related conditions (PMID: 30723320). 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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine