ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.383T>C (p.Val128Ala)

dbSNP: rs1566186839
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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 RCV000700453 SCV000829209 uncertain significance Retinoblastoma 2018-04-07 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 128 of the RB1 protein (p.Val128Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RB1-related disease. 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.
Ambry Genetics RCV004026513 SCV005034602 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-13 criteria provided, single submitter clinical testing The p.V128A variant (also known as c.383T>C), located in coding exon 4 of the RB1 gene, results from a T to C substitution at nucleotide position 383. The valine at codon 128 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.

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