NM_182548.4(LHFPL5):c.473G>A (p.Arg158Gln) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 3, 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:: RCV001898175.7

Allele description [Variation Report for NM_182548.4(LHFPL5):c.473G>A (p.Arg158Gln)]

NM_182548.4(LHFPL5):c.473G>A (p.Arg158Gln)

Gene:

LHFPL5:LHFPL tetraspan subfamily member 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.31

Genomic location:

Preferred name:

NM_182548.4(LHFPL5):c.473G>A (p.Arg158Gln)

HGVS:

NC_000006.12:g.35814606G>A
NG_012184.3:g.22401G>A
NM_182548.4:c.473G>AMANE SELECT
NP_872354.1:p.Arg158Gln
LRG_1352t1:c.473G>A
LRG_1352:g.22401G>A
LRG_1352p1:p.Arg158Gln
NC_000006.11:g.35782383G>A
NG_012184.2:g.14313G>A

Protein change:

R158Q

Links:

dbSNP: rs566829909

NCBI 1000 Genomes Browser:

rs566829909

Molecular consequence:

NM_182548.4:c.473G>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
SCV002157551	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 3, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26437881, 30298622, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002157551

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 3, 2023)

germline

clinical testing

PubMed (3)
[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

Clinical and molecular delineation of dysequilibrium syndrome type 2 and profound sensorineural hearing loss in an inbred Arab family.

Komara M, John A, Suleiman J, Ali BR, Al-Gazali L.

Am J Med Genet A. 2016 Feb;170A(2):540-543. doi: 10.1002/ajmg.a.37421. Epub 2015 Oct 5. No abstract available.

PubMed [citation]

PMID:: 26437881

High prevalence of congenital deafness on Reunion Island is due to a founder variant of LHFPL5.

Lerat J, Bonnet C, Cartault F, Loundon N, Jacquemont ML, Darcel F, Rouillon I, Mezouaghi K, Guichet A, Litzler J, Gesny R, Gherbi S, Aissa IB, Digeon FSJ, Garabedian EN, Bonnefont JP, Genin E, Denoyelle F, Jonard L, Marlin S.

Clin Genet. 2019 Jan;95(1):177-181. doi: 10.1111/cge.13460. Epub 2018 Nov 4.

PubMed [citation]

PMID:: 30298622

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002157551.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 158 of the LHFPL5 protein (p.Arg158Gln). This variant is present in population databases (rs566829909, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with LHFPL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1393163). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. This variant disrupts the p.Arg158 amino acid residue in LHFPL5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26437881, 30298622). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Sep 29, 2024

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