NM_000551.4(VHL):c.554A>G (p.Tyr185Cys) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 18, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000565491.6

Allele description [Variation Report for NM_000551.4(VHL):c.554A>G (p.Tyr185Cys)]

NM_000551.4(VHL):c.554A>G (p.Tyr185Cys)

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:

single nucleotide variant

Cytogenetic location:

3p25.3

Genomic location:

Preferred name:

NM_000551.4(VHL):c.554A>G (p.Tyr185Cys)

HGVS:

NC_000003.12:g.10149877A>G
NG_008212.3:g.13243A>G
NG_046756.1:g.7639A>G
NM_000551.4:c.554A>GMANE SELECT
NM_001354723.2:c.*108A>G
NM_198156.3:c.431A>G
NP_000542.1:p.Tyr185Cys
NP_000542.1:p.Tyr185Cys
NP_937799.1:p.Tyr144Cys
LRG_322t1:c.554A>G
LRG_322:g.13243A>G
LRG_322p1:p.Tyr185Cys
NC_000003.11:g.10191561A>G
NM_000551.3:c.554A>G
p.[Tyr185Cys]

Protein change:

Y144C

Links:

dbSNP: rs561874453

NCBI 1000 Genomes Browser:

rs561874453

Molecular consequence:

NM_001354723.2:c.*108A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000551.4:c.554A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.431A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

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Homo sapiens glutamate-ammonia ligase (GLUL), RefSeqGene on chromosome 1
Homo sapiens glutamate-ammonia ligase (GLUL), RefSeqGene on chromosome 1
gi|742670592|ref|NG_013347.2|

Nucleotide
S41 family peptidase [Shewanella oncorhynchi]
S41 family peptidase [Shewanella oncorhynchi]
gi|2566802745|gnl|PRJNA1005235|RA17 50|gb|WMB73103.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000675796	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Aug 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002534187	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Jan 25, 2022)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000675796

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Aug 18, 2022)

germline

clinical testing

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

Citation Link,

SCV002534187

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Jan 25, 2022)

germline

curation

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

Citation Link

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, curation

Citations

PubMed

Molecular subtypes of clear cell renal cell carcinoma are associated with sunitinib response in the metastatic setting.

Beuselinck B, Job S, Becht E, Karadimou A, Verkarre V, Couchy G, Giraldo N, Rioux-Leclercq N, Molinié V, Sibony M, Elaidi R, Teghom C, Patard JJ, Méjean A, Fridman WH, Sautès-Fridman C, de Reyniès A, Oudard S, Zucman-Rossi J.

Clin Cancer Res. 2015 Mar 15;21(6):1329-39. doi: 10.1158/1078-0432.CCR-14-1128. Epub 2015 Jan 12.

PubMed [citation]

PMID:: 25583177

Details of each submission

From Ambry Genetics, SCV000675796.5

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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

From Sema4, Sema4, SCV002534187.1

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

#	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 8, 2024

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