Submissions for variant NM_020975.6(RET):c.2996C>G (p.Ala999Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV003230330	SCV003928091	uncertain significance	Multiple endocrine neoplasia type 2A	2023-03-31	criteria provided, single submitter	clinical testing	The RET c.2996C>G (p.Ala999Gly) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with multiple endocrine neoplasia type II. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004538927	SCV004105594	uncertain significance	RET-related disorder	2023-07-16	criteria provided, single submitter	clinical testing	The RET c.2996C>G variant is predicted to result in the amino acid substitution p.Ala999Gly. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.