ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.203A>G (p.Tyr68Cys) (rs876660634)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215167 SCV000278224 pathogenic Hereditary cancer-predisposing syndrome 2018-02-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),Well-characterized mutation at same position,Other data supporting pathogenic classification,Rarity in general population databases (dbsnp, esp, 1000 genomes),Structural Evidence
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735377 SCV000854532 pathogenic Autistic disorder of childhood onset; Global developmental delay; Seizures; Cognitive impairment; Cortical visual impairment; Microcephaly; Developmental regression; Infantile spasms criteria provided, single submitter clinical testing
Invitae RCV000690989 SCV000818724 pathogenic PTEN hamartoma tumor syndrome 2018-04-09 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 68 of the PTEN protein (p.Tyr68Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Cowden syndrome (PMID: 19457929, 24778394, 26246517, 21956414). ClinVar contains an entry for this variant (Variation ID: 233777). Experimental studies have shown that this missense change affects the subcellular localization of PTEN, and inhibits its protein phosphatase activity (PMID: 19457929, 26246517). Other missense substitutions at this codon (p.Tyr68His and p.Tyr68Asp) have been reported in individuals affected with Cowden syndrome and have been determined to be pathogenic or likely pathogenic (PMID: 25669429, 9600246, 16704655, 20926450, 19457929). This suggests that the tyrosine residue is critical for PTEN protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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