ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.40A>G (p.Arg14Gly) (rs1085308047)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Herman Laboratory,Nationwide Children's Hospital RCV000490585 SCV000579273 pathogenic PTEN hamartoma tumor syndrome 2017-03-01 criteria provided, single submitter clinical testing
GeneDx RCV000492940 SCV000581704 not provided not provided no assertion provided clinical testing This A>G nucleotide substitution results in the replacement of an Arginine codon (AGG) with a Glycine codon (GGG) at amino acid position 14, and is denoted c.40A>G at the cDNA level or p.R14G at the protein level. The novel R14G missense change has not been published as a germline pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. However, the R14G amino acid substitution has previously been reported as a somatic change in two colon tumors and one kidney tumor among other tumor types according to the Catalogue of Somatic Mutations in Cancer. The NHLBI ESP Exome Sequencing Project reports R14G was not observed in approximately 6500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. The R14G variant is a non-conservative substitution as a positively-charged Arginine residue is replaced by a neutral Glycine residue at a position that is evolutionarily well-conserved. This amino acid substitution is located within the phosphatase tensin-type domain, a known functional domain. missense pathogenic variants in nearby positions have been reported in the literature, according to HGMD (K13E, R15S, D22G). Therefore, R14G is a strong candidate for a disease-causing mutation likely associated with a PTEN-related disorder; however the possibility that it is a benign variant cannot be excluded.

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