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NM_000551.4(VHL):c.302T>A (p.Leu101Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 6, 2022
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:
RCV002435996.2

Allele description [Variation Report for NM_000551.4(VHL):c.302T>A (p.Leu101Gln)]

NM_000551.4(VHL):c.302T>A (p.Leu101Gln)

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.302T>A (p.Leu101Gln)
HGVS:
  • NC_000003.12:g.10142149T>A
  • NG_008212.3:g.5515T>A
  • NM_000551.4:c.302T>AMANE SELECT
  • NM_001354723.2:c.302T>A
  • NM_198156.3:c.302T>A
  • NP_000542.1:p.Leu101Gln
  • NP_000542.1:p.Leu101Gln
  • NP_001341652.1:p.Leu101Gln
  • NP_937799.1:p.Leu101Gln
  • LRG_322t1:c.302T>A
  • LRG_322:g.5515T>A
  • LRG_322p1:p.Leu101Gln
  • NC_000003.11:g.10183833T>A
  • NM_000551.3:c.302T>A
  • NR_176335.1:n.372T>A
Protein change:
L101Q
Molecular consequence:
  • NM_000551.4:c.302T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354723.2:c.302T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198156.3:c.302T>A - 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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002753135Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jun 6, 2022) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV002753135.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.L101Q variant (also known as c.302T>A), located in coding exon 1 of the VHL gene, results from a T to A substitution at nucleotide position 302. The leucine at codon 101 is replaced by glutamine, an amino acid with dissimilar properties. Based on internal structural analysis, L101Q is disruptive to the local structure and is more disruptive that other nearly pathogenic variants in this region (Ambry internal data). Two other alterations at the same codon, p.L101P and p.L101R, have been detected in multiple patients with Von Hippel-Lindau disease (VHL) (Zbar, B et al. Hum Mutat. 1996;8(4):348-57; Rocha, JC et al. J Med Genet. 2003 Mar;40(3):e31; Taylor C et al. Int. J. Oncol., 2012 Oct;41:1229-40; Kim, HJ et al. Laryngoscope. 2013 Feb;123(2):477-83). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024