ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3180A>C (p.Lys1060Asn)

dbSNP: rs1361161086
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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 RCV001937768 SCV002179761 uncertain significance Multiple endocrine neoplasia, type 2 2023-09-01 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1060 of the RET protein (p.Lys1060Asn). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 1407322). 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002324313 SCV002609433 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-02 criteria provided, single submitter clinical testing The p.K1060N variant (also known as c.3180A>C), located in coding exon 19 of the RET gene, results from an A to C substitution at nucleotide position 3180. The lysine at codon 1060 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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 RCV001937768 SCV004829513 uncertain significance Multiple endocrine neoplasia, type 2 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces lysine with asparagine at codon 1060 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 RET-related disorders in the literature. This variant has been identified in 1/251034 chromosomes 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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