Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000551.4(VHL):c.422dup (p.Asn141fs)

CA16611276

411979 (ClinVar)

Gene: VHL
Condition: von Hippel-Lindau disease
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3edb89db-b42c-4081-a05d-026362ccc657
Approved on: 2024-06-25
Published on: 2024-06-25

HGVS expressions

NM_000551.4:c.422dup
NM_000551.4(VHL):c.422dup (p.Asn141fs)
NC_000003.12:g.10146595dup
CM000665.2:g.10146595dup
NC_000003.11:g.10188279dup
CM000665.1:g.10188279dup
NC_000003.10:g.10163279dup
NG_008212.3:g.9961dup
ENST00000696142.1:c.*99dup
ENST00000696143.1:c.600-3192dup
ENST00000696153.1:c.422dup
ENST00000256474.3:c.422dup
ENST00000256474.2:c.422dup
ENST00000345392.2:c.341-3192dup
ENST00000477538.1:n.558dup
NM_000551.3:c.422dup
NM_198156.2:c.341-3192dup
NM_001354723.1:c.*18-3192dup
NM_001354723.2:c.*18-3192dup
NM_198156.3:c.341-3192dup
More

Pathogenic

Met criteria codes 3
PS4_Supporting PM2_Supporting PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen VHL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for VHL Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
VHL VCEP
The NM_000551.4(VHL):c.422dup (p.Asn141fs) is a frameshift variant affecting position 141. This variant is not expected to undergo nonsense mediated decay, but is in a functional domain critical to the protein function (nuclear export domain) (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). Two commercial laboratories report cases. Case 1 (0.5 points): displayed bilateral renal masses and likely pheochromocytoma, with a small Paraganglioma panel run. Case 2 (0.5): Multiple renal tumors in 40s, no other family history known, and a 13-gene panel was run for renal cancers (PS4_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal-dominant von Hippel Lindau syndrome (VHL syndrome) based on the ACMG/AMP criteria applied, as specified by the ClinGen VHL VCEP Version 1.0 (Specifications approval date: 02/26/2024. Variant Approval Date 06/25/2024).
Met criteria codes
PS4_Supporting
Two commercial laboratories report cases. Case 1 (0.5 points): displayed bilateral renal masses and likely pheochromocytoma, with a small Paraganglioma panel run. Case 2 (0.5 points): Multiple renal tumors in 40s, no other family history known. Subject had a 13-gene panel for renal cancers.
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PVS1
This variant is not expected to undergo nonsense mediated decay, but is in a functional domain critical to the protein function (nuclear export domain) (PVS1).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.