Submissions for variant NM_000321.3(RB1):c.941T>C (p.Val314Ala)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002373985	SCV002685021	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-02	criteria provided, single submitter	clinical testing	The p.V314A variant (also known as c.941T>C), located in coding exon 10 of the RB1 gene, results from a T to C substitution at nucleotide position 941. The valine at codon 314 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003103585	SCV003511859	uncertain significance	Retinoblastoma	2022-10-13	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with RB1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 314 of the RB1 protein (p.Val314Ala).
All of Us Research Program, National Institutes of Health	RCV003103585	SCV004844639	uncertain significance	Retinoblastoma	2024-01-11	criteria provided, single submitter	clinical testing	This missense variant replaces valine with alanine at codon 314 of the RB1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31390 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.