ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.436A>C (p.Asn146His)

dbSNP: rs1266294051
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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 RCV002027161 SCV002312906 uncertain significance Retinoblastoma 2021-11-19 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 146 of the RB1 protein (p.Asn146His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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 RCV002331637 SCV002632278 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-30 criteria provided, single submitter clinical testing The p.N146H variant (also known as c.436A>C), located in coding exon 4 of the RB1 gene, results from an A to C substitution at nucleotide position 436. The asparagine at codon 146 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. 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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