ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.947T>C (p.Leu316Pro) (rs1064793345)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV001078166 SCV001244235 uncertain significance PTEN hamartoma tumor syndrome 2019-11-22 reviewed by expert panel curation PTEN c.947T>C (p.Leu316Pro) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 30311381)
GeneDx RCV000480591 SCV000565874 uncertain significance not provided 2017-03-24 criteria provided, single submitter clinical testing The L316P variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L316P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and is located within the C2 domain (Wang et al., 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, we consider L316P to be a variant of uncertain significance.
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000678387 SCV000804456 likely pathogenic Macrocephaly/autism syndrome; Cowden syndrome 1 2017-05-04 criteria provided, single submitter provider interpretation This 6 year old male with macrocephaly and autism was found to carry a paternally inherited missense variant in the PTEN gene. His father is noted to have macrocephaly, dysfluency, and a learning disability. The patient's brother also carries the PTEN variant and has macrocephaly and a history of a speech delay. The patient had a normal thyroid ultrasound at age 6. Computational models predict the variant to be damaging. The variant is absent from population databases. Based on how the variant is segregating with macrocephaly and neurodevelopmental disorders in the family, the variant is felt to be likely pathogenic.

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