ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2982A>C (p.Lys994Asn) (rs199718928)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411986 SCV000489943 uncertain significance Multiple endocrine neoplasia, type 2b 2016-08-16 criteria provided, single submitter clinical testing
Counsyl RCV000409131 SCV000489944 uncertain significance Multiple endocrine neoplasia, type 2a 2016-08-16 criteria provided, single submitter clinical testing
Invitae RCV000458385 SCV000543839 uncertain significance Multiple endocrine neoplasia, type 2 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 994 of the RET protein (p.Lys994Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs199718928, ExAC 0.001%). This variant has been reported in the literature in an individual with ependymoma (PMID: 26580448). ClinVar contains an entry for this variant (Variation ID: 41843). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000568654 SCV000674750 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-22 criteria provided, single submitter clinical testing Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000763651 SCV000894531 uncertain significance Congenital central hypoventilation; Hirschsprung disease 1; Multiple endocrine neoplasia, type 2b; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia, type 2a 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001104857 SCV001261752 uncertain significance Multiple endocrine neoplasia 2019-01-11 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001104858 SCV001261753 uncertain significance Renal hypodysplasia/aplasia 1 2019-01-11 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001104859 SCV001261754 uncertain significance Pheochromocytoma 2019-01-11 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001104860 SCV001261755 uncertain significance Hirschsprung disease 1 2019-01-11 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034775 SCV000043480 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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