NM_000551.4(VHL):c.3G>T (p.Met1Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 20, 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:: RCV000562501.8

Allele description [Variation Report for NM_000551.4(VHL):c.3G>T (p.Met1Ile)]

NM_000551.4(VHL):c.3G>T (p.Met1Ile)

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.3G>T (p.Met1Ile)

HGVS:

NC_000003.12:g.10141850G>T
NG_008212.3:g.5216G>T
NM_000551.4:c.3G>TMANE SELECT
NM_001354723.2:c.3G>T
NM_198156.3:c.3G>T
NP_000542.1:p.Met1Ile
NP_000542.1:p.Met1Ile
NP_001341652.1:p.Met1Ile
NP_937799.1:p.Met1Ile
LRG_322t1:c.3G>T
LRG_322:g.5216G>T
LRG_322p1:p.Met1Ile
NC_000003.11:g.10183534G>T
NM_000551.3:c.3G>T

Protein change:

M1I

Links:

dbSNP: rs578091032

NCBI 1000 Genomes Browser:

rs578091032

Molecular consequence:

NM_000551.4:c.3G>T - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001354723.2:c.3G>T - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_198156.3:c.3G>T - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000551.4:c.3G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354723.2:c.3G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198156.3:c.3G>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
SCV000675801	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Aug 20, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9671762, 9751722 Citation Link,
SCV002534172	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Feb 19, 2022)	germline	curation	PubMed (5) [See all records that cite these PMIDs] 30093976, 33840814, 9671762, 9751722, 23541568 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000675801

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Aug 20, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002534172

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Feb 19, 2022)

germline

curation

PubMed (5)
[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

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers.

Chan GHJ, Ong PY, Low JJH, Kong HL, Ow SGW, Tan DSP, Lim YW, Lim SE, Lee SC.

Oncotarget. 2018 Jul 17;9(55):30649-30660. doi: 10.18632/oncotarget.25769.

PubMed [citation]

PMID:: 30093976
PMCID:: PMC6078133

Comprehensive germline-genomic and clinical profiling in 160 unselected children and adolescents with cancer.

Wagener R, Taeubner J, Walter C, Yasin L, Alzoubi D, Bartenhagen C, Attarbaschi A, Classen CF, Kontny U, Hauer J, Fischer U, Dugas M, Kuhlen M, Borkhardt A, Brozou T.

Eur J Hum Genet. 2021 Aug;29(8):1301-1311. doi: 10.1038/s41431-021-00878-x. Epub 2021 Apr 12.

PubMed [citation]

PMID:: 33840814
PMCID:: PMC8385053

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000675801.6

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

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, SCV002534172.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (5)

#	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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