ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1892A>T (p.Asp631Val)

dbSNP: rs121913308
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001362386 SCV001558398 uncertain significance Multiple endocrine neoplasia, type 2 2020-02-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 631 of the RET protein (p.Asp631Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with pheochromocytoma (PMID: 15858153). ClinVar contains an entry for this variant (Variation ID: 24917, 549800). 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: "Benign"; Align-GVGD: "Class C0"). This variant disrupts the p.Asp631 amino acid residue in RET. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16839264, 10049754, 22274720, 28747092). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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