NM_022437.3(ABCG8):c.1949T>G (p.Leu650Arg) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 13, 2021
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:: RCV001870437.5

Allele description [Variation Report for NM_022437.3(ABCG8):c.1949T>G (p.Leu650Arg)]

NM_022437.3(ABCG8):c.1949T>G (p.Leu650Arg)

Gene:

ABCG8:ATP binding cassette subfamily G member 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_022437.3(ABCG8):c.1949T>G (p.Leu650Arg)

HGVS:

NC_000002.12:g.43877840T>G
NG_008884.2:g.50899T>G
NM_001357321.2:c.1946T>G
NM_022437.3:c.1949T>GMANE SELECT
NP_001344250.1:p.Leu649Arg
NP_071882.1:p.Leu650Arg
LRG_1182t1:c.1949T>G
LRG_1182:g.50899T>G
LRG_1182p1:p.Leu650Arg
NC_000002.11:g.44104979T>G

Protein change:

L649R

Links:

dbSNP: rs1209143268

NCBI 1000 Genomes Browser:

rs1209143268

Molecular consequence:

NM_001357321.2:c.1946T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_022437.3:c.1949T>G - 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
SCV002123408	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 13, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25056759, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002123408

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 13, 2021)

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

Potential effects of NPC1L1 polymorphisms in protecting against clinical disease in a chinese family with sitosterolaemia.

Hu M, Yuen YP, Kwok JS, Griffith JF, Tomlinson B.

J Atheroscler Thromb. 2014;21(9):989-95. Epub 2014 Jul 24.

PubMed [citation]

PMID:: 25056759

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 Invitae, SCV002123408.3

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

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 650 of the ABCG8 protein (p.Leu650Arg). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant has been observed in individual(s) with sitosterolemia (PMID: 25056759). It has also been observed to segregate with disease in related individuals. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0").

#	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: Mar 5, 2024

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