NM_000551.4(VHL):c.241C>T (p.Pro81Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 25, 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:: RCV000115744.20

Allele description [Variation Report for NM_000551.4(VHL):c.241C>T (p.Pro81Ser)]

NM_000551.4(VHL):c.241C>T (p.Pro81Ser)

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.241C>T (p.Pro81Ser)

Other names:

p.P81S:CCG>TCG; NM_000551.4(VHL):c.241C>T

HGVS:

NC_000003.12:g.10142088C>T
NG_008212.3:g.5454C>T
NM_000551.4:c.241C>TMANE SELECT
NM_001354723.2:c.241C>T
NM_198156.3:c.241C>T
NP_000542.1:p.Pro81Ser
NP_000542.1:p.Pro81Ser
NP_001341652.1:p.Pro81Ser
NP_937799.1:p.Pro81Ser
LRG_322t1:c.241C>T
LRG_322:g.5454C>T
LRG_322p1:p.Pro81Ser
NC_000003.11:g.10183772C>T
NM_000551.2:c.241C>T
NM_000551.3:c.241C>T
P40337:p.Pro81Ser
p.P81S
p.[Pro81Ser]

Protein change:

P81S; PRO81SER

Links:

UniProtKB: P40337#VAR_005689; OMIM: 608537.0020; dbSNP: rs104893829

NCBI 1000 Genomes Browser:

rs104893829

Molecular consequence:

NM_000551.4:c.241C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.241C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.241C>T - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000212872	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Mar 22, 2021)	germline	clinical testing	PubMed (14) [See all records that cite these PMIDs] 10567493, 11106358, 11739384, 19228690, 19906784, 20447124, 23990664, 23990666, 25637381, 28503092, 29790589, 8634692, 8956040, 9829911 Citation Link,
SCV002534150	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Jan 25, 2022)	germline	curation	PubMed (14) [See all records that cite these PMIDs] 11106358, 8634692, 9829911, 19906784, 28503092, 27527340, 30877234, 7563486, 8772572, 12414898, 25637381, 19228690, 22234250, 23990666 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000212872

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Mar 22, 2021)

germline

clinical testing

PubMed (14)
[See all records that cite these PMIDs]

Citation Link,

SCV002534150

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Jan 25, 2022)

germline

curation

PubMed (14)
[See all records that cite these PMIDs]

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

The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system.

Gläsker S, Bender BU, Apel TW, Natt E, van Velthoven V, Scheremet R, Zentner J, Neumann HP.

J Neurol Neurosurg Psychiatry. 1999 Dec;67(6):758-62.

PubMed [citation]

PMID:: 10567493
PMCID:: PMC1736691

Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein.

Li Z, Na X, Wang D, Schoen SR, Messing EM, Wu G.

J Biol Chem. 2002 Feb 15;277(7):4656-62. Epub 2001 Dec 5.

PubMed [citation]

PMID:: 11739384

See all PubMed Citations (20)

Details of each submission

From Ambry Genetics, SCV000212872.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (14)

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, SCV002534150.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (14)

#	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 8, 2024

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