ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1030G>A (p.Gly344Ser)

gnomAD frequency: 0.00001  dbSNP: rs749883001
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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 RCV001040633 SCV001204218 uncertain significance Multiple endocrine neoplasia, type 2 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 344 of the RET protein (p.Gly344Ser). This variant is present in population databases (rs749883001, gnomAD 0.0009%). This missense change has been observed in individual(s) with sporadic Hirschsprung disease (PMID: 30217742). ClinVar contains an entry for this variant (Variation ID: 838975). 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 RCV002379500 SCV002698042 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-23 criteria provided, single submitter clinical testing The p.G344S variant (also known as c.1030G>A), located in coding exon 5 of the RET gene, results from a G to A substitution at nucleotide position 1030. The glycine at codon 344 is replaced by serine, an amino acid with similar properties. This alteration was identified in 1 individual in a cohort of patients with short-segment Hirschsprung disease and 0 controls (Tang CS et al. Gastroenterology, 2018 12;155:1908-1922.e5).This amino acid position is not well 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.
Baylor Genetics RCV003467724 SCV004208676 uncertain significance Hirschsprung disease, susceptibility to, 1 2023-09-26 criteria provided, single submitter clinical testing

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