NM_001256789.3(CACNA1F):c.2959C>T (p.Arg987Trp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 17, 2022
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:: RCV003112448.5

Allele description [Variation Report for NM_001256789.3(CACNA1F):c.2959C>T (p.Arg987Trp)]

NM_001256789.3(CACNA1F):c.2959C>T (p.Arg987Trp)

Gene:

CACNA1F:calcium voltage-gated channel subunit alpha1 F [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_001256789.3(CACNA1F):c.2959C>T (p.Arg987Trp)

HGVS:

NC_000023.11:g.49217975G>A
NG_009095.2:g.20392C>T
NM_001256789.3:c.2959C>TMANE SELECT
NM_001256790.3:c.2797C>T
NM_005183.3:c.2992C>T
NM_005183.4:c.2992C>T
NP_001243718.1:p.Arg987Trp
NP_001243719.1:p.Arg933Trp
NP_005174.2:p.Arg998Trp
NC_000023.10:g.49074434G>A

Protein change:

R933W

Molecular consequence:

NM_001256789.3:c.2959C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001256790.3:c.2797C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005183.4:c.2992C>T - 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
SCV003787217	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30825406, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003787217

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 17, 2022)

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

Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F-mediated inherited retinal disorders.

Zeitz C, Michiels C, Neuillé M, Friedburg C, Condroyer C, Boyard F, Antonio A, Bouzidi N, Milicevic D, Veaux R, Tourville A, Zoumba A, Seneina I, Foussard M, Andrieu C, N Preising M, Blanchard S, Saraiva JP, Mesrob L, Le Floch E, Jubin C, Meyer V, et al.

Hum Mutat. 2019 Jun;40(6):765-787. doi: 10.1002/humu.23735. Epub 2019 Mar 28.

PubMed [citation]

PMID:: 30825406

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, SCV003787217.3

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1F protein function. This missense change has been observed in individual(s) with incomplete congenital stationary night blindness (PMID: 30825406). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 998 of the CACNA1F protein (p.Arg998Trp).

#	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 13, 2024

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