ClinVar Miner

Submissions for variant NM_020975.6(RET):c.667G>A (p.Val223Met)

gnomAD frequency: 0.00001  dbSNP: rs587780815
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123324 SCV000166631 uncertain significance Multiple endocrine neoplasia, type 2 2022-09-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 223 of the RET protein (p.Val223Met). This variant is present in population databases (rs587780815, gnomAD 0.01%). This missense change has been observed in individual(s) with bilateral renal hypodysplasia (PMID: 24429398). ClinVar contains an entry for this variant (Variation ID: 136122). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV000411929 SCV000489823 uncertain significance Multiple endocrine neoplasia, type 2b 2016-05-03 criteria provided, single submitter clinical testing
Counsyl RCV000409553 SCV000489824 uncertain significance Multiple endocrine neoplasia, type 2a 2016-05-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV001025526 SCV001187728 likely benign Hereditary cancer-predisposing syndrome 2023-07-28 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002251993 SCV002523998 uncertain significance See cases 2021-09-03 criteria provided, single submitter clinical testing ACMG classification criteria: PP3
Sema4, Sema4 RCV001025526 SCV002527921 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-22 criteria provided, single submitter curation

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