ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.1072C>T (p.Arg358Ter) (rs121913301)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725187 SCV000334770 pathogenic not provided 2015-09-02 criteria provided, single submitter clinical testing
Invitae RCV000013951 SCV000551815 pathogenic Retinoblastoma 2020-06-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg358*) in the RB1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with unilateral or bilateral retinoblastoma (PMID: 22328814, 7795591, 25928201, 27582626, 22219649, 24078560, 24791139, 26530098). ClinVar contains an entry for this variant (Variation ID: 13076). Loss-of-function variants in RB1 are known to be pathogenic (PMID: 17096365). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000492492 SCV000580766 pathogenic Hereditary cancer-predisposing syndrome 2019-03-11 criteria provided, single submitter clinical testing The p.R358* pathogenic mutation (also known as c.1072C>T), located in coding exon 11 of the RB1 gene, results from a C to T substitution at nucleotide position 1072. This changes the amino acid from an arginine to a stop codon within coding exon 11. This mutation has been reported in numerous unrelated individuals diagnosed with both unilateral and bilateral retinoblastoma (Blanquet V et al. Hum. Mol. Genet. 1995 Mar;4:383-8; Dommering CJ et al. J. Med. Genet. 2014 Jun;51:366-74; Devarajan B et al. BMC Cancer 2015 Apr;15:320; Sagi M et al. Fam. Cancer 2015 Sep;14:471-80; Kalsoom S et al. Mol. Vis. 2015 Sep;21:1085-92). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000013951 SCV000853201 pathogenic Retinoblastoma 2016-05-11 criteria provided, single submitter clinical testing This is a nonsense alteration in which a C is replaced by a T at coding position 1072 and is predicted to change an Arginine to a premature stop codon at codon 358.
OMIM RCV000013951 SCV000034198 pathogenic Retinoblastoma 1989-12-21 no assertion criteria provided literature only
Genetic Diagnostic Laboratory,University of Pennsylvania School of Medicine RCV000013951 SCV000087370 pathogenic Retinoblastoma 2013-09-16 no assertion criteria provided research
Database of Curated Mutations (DoCM) RCV000013951 SCV000504838 likely pathogenic Retinoblastoma 2015-07-14 no assertion criteria provided literature only

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