ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.256C>G (p.Pro86Ala) (rs398123481)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000079208 SCV000264683 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723702 SCV000111078 pathogenic not provided 2013-07-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000079208 SCV000697489 likely pathogenic Von Hippel-Lindau syndrome 2016-01-29 criteria provided, single submitter clinical testing Variant summary: This c.256C>G variant affects a conserved nucleotide, resulting in amino acid change from Pro to Ala in HIFalfa domain of VHL protein. 4/4 in-silico tools predict this variant to be damaging. This variant was found in 2/102226 control chromosomes including the broad and large population from ExAC at a frequency of 0.0000196, which is lower than the maximal expected frequency of a pathogenic allele (0.0000208) in this gene. In literature, this variant has been reported in five independent patients with Von Hippel-Lindau disease or related cancers. Other missense changes at this codon are also reported in association VHL disease, namely p.P86R, p.P86L and p.P86S, suggesting that this codon is likely to be a mutational hot-spot. One clinical lab (via ClinVar) and one reputable database classify this variant as pathogenic. Taken together, this variant is currently classified as Likely Pathogenic.

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