ClinVar Miner

Submissions for variant NM_016111.4(TELO2):c.1100G>T (p.Cys367Phe) (rs202020308)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University RCV000225284 SCV000298024 pathogenic You-Hoover-Fong syndrome criteria provided, single submitter research
Fulgent Genetics,Fulgent Genetics RCV000225284 SCV000893394 likely pathogenic You-Hoover-Fong syndrome 2018-10-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826054 SCV000967548 uncertain significance not specified 2018-04-12 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Cys367Phe variant in TELO2 has been reported in the 2 individuals with intellectual disab ility and segregated in 2 affected family members from one family (You 2016). Al l of these individuals were compound heterozygous. This variant has also been re ported in ClinVar (Variation ID: 236225). This variant has been identified in 0. 06% (19/33748) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs202020308). Although this variant has been seen in the general population, its frequency is low enough to be consiste nt with a recessive carrier frequency. Computational prediction tools and conser vation analysis suggest that the p.Cys367Phe variant may impact the protein, tho ugh this information is not predictive enough to determine pathogenicity. Functi onal studies provide some evidence that the p.Cys367Phe variant may impact prote in function (You 2016). However, these types of assays may not accurately repres ent biological function. In summary, while there is some suspicion for a pathoge nic role, the clinical significance of the p.Cys367Phe variant is uncertain. ACM G/AMP Criteria applied: PP1; PP3; PS3_Supporting, PM1_Supporting, PM3_Supporting
UNC Molecular Genetics Laboratory,University of North Carolina at Chapel Hill RCV000225284 SCV001423845 likely pathogenic You-Hoover-Fong syndrome criteria provided, single submitter research The TELO2 c.1100G>T likely pathogenic missense variant changes a single amino acid in the protein coding region from a cysteine to a phenylalanine. This variant has been reported to segregate with You-Hoover-Fong syndrome in two families and alters an amino acid conserved in vertebrates located within the TTI1 binding domain (PMID: 27132593).
OMIM RCV000225284 SCV000282066 pathogenic You-Hoover-Fong syndrome 2019-09-10 no assertion criteria provided literature only
PerkinElmer Genomics RCV000225284 SCV002016874 likely pathogenic You-Hoover-Fong syndrome 2019-12-31 no assertion criteria provided clinical testing

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