ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.340+695_340+702dup

dbSNP: rs1381868678
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001352380 SCV001546927 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-11-09 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the VHL gene. It is not expected to change the encoded amino acid sequence of the VHL protein. However, this sequence change falls within a cryptic exon in the VHL gene, known as exon E1’, which is naturally expressed at low levels in several human tissues (PMID: 29891534). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1047639). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV003946013 SCV004763430 uncertain significance VHL-related disorder 2024-07-30 no assertion criteria provided clinical testing The VHL c.460_467dup8 variant is predicted to result in a frameshift and premature protein termination (p.Asp156Glufs*11). Using an alternate transcript (NM_000551.4), which is present in the Human Gene Mutation Database (HGMD), this variant is an intronic change that is not predicted to impact splicing (c.340+695_340+702dup). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of European (non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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