ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2027T>C (p.Leu676Ser)

dbSNP: rs1566235448
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000709348 SCV000838925 uncertain significance Retinoblastoma 2018-07-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000709348 SCV001393034 uncertain significance Retinoblastoma 2019-07-23 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 584872). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 676 of the RB1 protein (p.Leu676Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine.
Ambry Genetics RCV004026781 SCV005034522 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-11 criteria provided, single submitter clinical testing The p.L676S variant (also known as c.2027T>C), located in coding exon 20 of the RB1 gene, results from a T to C substitution at nucleotide position 2027. The leucine at codon 676 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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