ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.182A>G (p.His61Arg) (rs398123316)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Herman Laboratory,Nationwide Children's Hospital RCV000490582 SCV000579264 pathogenic PTEN hamartoma tumor syndrome 2017-03-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491953 SCV000579972 likely pathogenic Hereditary cancer-predisposing syndrome 2019-10-10 criteria provided, single submitter clinical testing ​The p.H61R variant (also known as c.182A>G) is located in coding exon 3 of the PTEN gene. This alteration results from an A to G substitution at nucleotide position 182. The histidine at codon 61 is replaced by arginine, an amino acid with similar properties. This alteration has been reported in individuals meeting relaxed International Cowden Consortium operational criteria for Cowden syndrome (Tan MH et al. Am J Hum Genet. 2011 Jan 7;88(1):42-56), as well as an individual with Bannayan-Riley-Ruvalcaba syndrome (Hansen-Kiss E et al. J. Med. Genet. 2017 07;54:471-478). Another mutation has also been reported at the same codon (p.H61D) in an individual with macrocephaly, ventricular dilatation, and features of VATER association (Reardon W et al. J Med Genet. 2001 Dec;38(12):820-3). This amino acid position is completely conserved on sequence alignment. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV000490582 SCV001499509 uncertain significance PTEN hamartoma tumor syndrome 2020-08-31 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 61 of the PTEN protein (p.His61Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome (PMID: 28526761, 21194675, 21659347, 20600018). ClinVar contains an entry for this variant (Variation ID: 189402). This variant has been reported to affect PTEN protein function (PMID: 10866302). 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.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785574 SCV000924147 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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