ClinVar Miner

Submissions for variant NM_020975.6(RET):c.972G>C (p.Trp324Cys) (rs758298916)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000167906 SCV000218554 uncertain significance Multiple endocrine neoplasia, type 2 2019-10-16 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 324 of the RET protein (p.Trp324Cys). The tryptophan residue is moderately conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is present in population databases (rs758298916, ExAC 0.006%). This variant has been reported in the literature in an individual affected with Hirschsprung disease (PMID: 11955539). ClinVar contains an entry for this variant (Variation ID: 188078). 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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 RCV000409785 SCV000490073 uncertain significance Multiple endocrine neoplasia, type 2b 2016-10-27 criteria provided, single submitter clinical testing
Counsyl RCV000410975 SCV000490074 uncertain significance Multiple endocrine neoplasia, type 2a 2016-10-27 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000994377 SCV001147864 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001107611 SCV001264777 likely benign Multiple endocrine neoplasia 2017-04-28 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001107612 SCV001264778 uncertain significance Renal hypodysplasia/aplasia 1 2017-04-28 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001107613 SCV001264779 uncertain significance Hirschsprung disease 1 2017-04-28 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 RCV001107614 SCV001264780 uncertain significance Pheochromocytoma 2017-04-28 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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