ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.984T>A (p.Asn328Lys)

dbSNP: rs1952716275
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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 RCV001306965 SCV001496356 uncertain significance Retinoblastoma 2023-07-19 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1009471). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RB1 protein function. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 328 of the RB1 protein (p.Asn328Lys).
Ambry Genetics RCV002384377 SCV002693208 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-04 criteria provided, single submitter clinical testing The p.N328K variant (also known as c.984T>A), located in coding exon 10 of the RB1 gene, results from a T to A substitution at nucleotide position 984. The asparagine at codon 328 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in an individual with a personal history of unilateral retinoblastoma diagnosed at 22 months (Rodríguez-Martín C et al. J Hum Genet, 2020 Jan;65:165-174). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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