NM_000551.4(VHL):c.379_380insCAG (p.Asp126_Gly127insAla) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 2018
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:: RCV000701611.7

Allele description [Variation Report for NM_000551.4(VHL):c.379_380insCAG (p.Asp126_Gly127insAla)]

NM_000551.4(VHL):c.379_380insCAG (p.Asp126_Gly127insAla)

Genes:

LOC107303340:3p25 von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase Alu-mediated recombination region [Gene]
VHL:von Hippel-Lindau tumor suppressor [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.379_380insCAG (p.Asp126_Gly127insAla)

HGVS:

NC_000003.12:g.10146552_10146553insCAG
NG_008212.3:g.9918_9919insCAG
NG_046756.1:g.4314_4315insCAG
NM_000551.4:c.379_380insCAGMANE SELECT
NM_001354723.2:c.*18-3235_*18-3234insCAG
NM_198156.3:c.341-3235_341-3234insCAG
NP_000542.1:p.Asp126_Gly127insAla
NP_000542.1:p.Gly127_Leu128insAla
LRG_322t1:c.379_380insCAG
LRG_322:g.9918_9919insCAG
LRG_322p1:p.Gly127_Leu128insAla
NC_000003.11:g.10188235_10188236insGCA
NC_000003.11:g.10188236_10188237insCAG
NM_000551.3:c.379_380insCAG

Links:

dbSNP: rs1559428103

NCBI 1000 Genomes Browser:

rs1559428103

Molecular consequence:

NM_000551.4:c.379_380insCAG - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001354723.2:c.*18-3235_*18-3234insCAG - intron variant - [Sequence Ontology: SO:0001627]
NM_198156.3:c.341-3235_341-3234insCAG - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Chuvash polycythemia
Synonyms:: POLYCYTHEMIA, VHL-DEPENDENT; Erythrocytosis, familial, 2
Identifiers:: MONDO: MONDO:0009892; MedGen: C1837915; Orphanet: 238557; OMIM: 263400

Name:: Von Hippel-Lindau syndrome (VHLS)
Synonyms:: VHL syndrome; Von Hippel-Lindau
Identifiers:: MONDO: MONDO:0008667; MedGen: C0019562; Orphanet: 892; OMIM: 193300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000830421	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 22, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000830421

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 22, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV000830421.4

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

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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the disrupted amino acids is currently unknown. This variant has not been reported in the literature in individuals with VHL-related disease. This variant is not present in population databases (ExAC no frequency). This variant, c.379_380insCAG, results in the insertion of 1 amino acid(s) to the VHL protein (p.Asp126_Gly127insAla), but otherwise preserves the integrity of the reading frame.

#	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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