ClinVar Miner

Submissions for variant NM_000481.4(AMT):c.752C>G (p.Pro251Arg)

gnomAD frequency: 0.00004  dbSNP: rs770999859
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666903 SCV000791275 uncertain significance Non-ketotic hyperglycinemia 2017-05-15 criteria provided, single submitter clinical testing
Invitae RCV000666903 SCV000828108 uncertain significance Non-ketotic hyperglycinemia 2022-05-06 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 251 of the AMT protein (p.Pro251Arg). This variant is present in population databases (rs770999859, gnomAD 0.02%). This missense change has been observed in individual(s) with non-syndromic myelomeningocele (PMID: 27620832). ClinVar contains an entry for this variant (Variation ID: 551763). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AMT protein function. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002232633 SCV002511514 uncertain significance not specified 2022-04-25 criteria provided, single submitter clinical testing Variant summary: AMT c.752C>G (p.Pro251Arg) results in a non-conservative amino acid change located in the Aminomethyltransferase, folate-binding domain of the encoded protein sequence. The variant allele was found at a frequency of 3.6e-05 in 251304 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.752C>G has been reported in the literature in one individual affected with Myelomeningocele. This report does not provide unequivocal conclusions about association of the variant with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV000666903 SCV001456312 uncertain significance Non-ketotic hyperglycinemia 2020-09-16 no assertion criteria provided clinical testing

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