ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1150C>G (p.Pro384Ala)

gnomAD frequency: 0.00006  dbSNP: rs536298339
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197885 SCV000255042 uncertain significance Multiple endocrine neoplasia, type 2 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 384 of the RET protein (p.Pro384Ala). This variant is present in population databases (rs536298339, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 216713). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Counsyl RCV000412082 SCV000489895 uncertain significance Multiple endocrine neoplasia, type 2b 2016-07-14 criteria provided, single submitter clinical testing
Counsyl RCV000410243 SCV000489896 uncertain significance Multiple endocrine neoplasia, type 2a 2016-07-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000567892 SCV000674890 benign Hereditary cancer-predisposing syndrome 2023-04-25 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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