ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3040G>A (p.Asp1014Asn)

gnomAD frequency: 0.00001  dbSNP: rs1371047639
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000803728 SCV000943612 uncertain significance Multiple endocrine neoplasia, type 2 2023-09-05 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with RET-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1014 of the RET protein (p.Asp1014Asn). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 648907). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics RCV002442678 SCV002753971 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-17 criteria provided, single submitter clinical testing The p.D1014N variant (also known as c.3040G>A) is located in coding exon 19 of the RET gene. The aspartic acid at codon 1014 is replaced by asparagine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 19. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV000803728 SCV004838710 uncertain significance Multiple endocrine neoplasia, type 2 2023-03-23 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 1014 of the RET protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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