ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3142C>G (p.Leu1048Val)

dbSNP: rs774347808
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410987 SCV000489785 uncertain significance Multiple endocrine neoplasia, type 2b 2016-02-12 criteria provided, single submitter clinical testing
Counsyl RCV000412050 SCV000489786 uncertain significance Multiple endocrine neoplasia, type 2a 2016-02-12 criteria provided, single submitter clinical testing
Invitae RCV000474558 SCV000543844 uncertain significance Multiple endocrine neoplasia, type 2 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1048 of the RET protein (p.Leu1048Val). This variant is present in population databases (rs774347808, gnomAD 0.003%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 22648184). ClinVar contains an entry for this variant (Variation ID: 372080). 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. 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 RCV000574881 SCV000674751 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-28 criteria provided, single submitter clinical testing The p.L1048V variant (also known as c.3142C>G), located in coding exon 19 of the RET gene, results from a C to G substitution at nucleotide position 3142. The leucine at codon 1048 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in an individual with Hirschsprung disease (Carter TC et al. J. Hum. Genet., 2012 Aug;57:485-93). 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.
GeneDx RCV003235199 SCV003933570 uncertain significance not provided 2022-12-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with Hirschprung disease (Carter et al., 2012); This variant is associated with the following publications: (PMID: 22648184, 14633923, 30034242, 29617658)

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