ClinVar Miner

Submissions for variant NM_020975.6(RET):c.815T>C (p.Phe272Ser)

dbSNP: rs2132708113
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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 RCV001938125 SCV002185204 uncertain significance Multiple endocrine neoplasia, type 2 2022-05-26 criteria provided, single submitter clinical testing 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 C0"). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 272 of the RET protein (p.Phe272Ser).
Ambry Genetics RCV002423021 SCV002679593 uncertain significance Hereditary cancer-predisposing syndrome 2015-11-17 criteria provided, single submitter clinical testing The p.F272S variant (also known as c.815T>C), located in coding exon 4 of the RET gene, results from a T to C substitution at nucleotide position 815. The phenylalanine at codon 272 is replaced by serine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6496 samples (12992 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 10000 alleles tested) in our clinical cohort. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.F272S remains unclear.

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