ClinVar Miner

Submissions for variant NM_000481.4(AMT):c.436G>A (p.Ala146Thr)

gnomAD frequency: 0.00005  dbSNP: rs570868528
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000638275 SCV000759768 uncertain significance Glycine encephalopathy 2024-12-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 146 of the AMT protein (p.Ala146Thr). This variant is present in population databases (rs570868528, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with AMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 531768). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt AMT protein function with a positive predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV000638275 SCV002798244 uncertain significance Glycine encephalopathy 2022-01-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV003243225 SCV003952618 uncertain significance Inborn genetic diseases 2023-03-29 criteria provided, single submitter clinical testing The c.436G>A (p.A146T) alteration is located in exon 4 (coding exon 4) of the AMT gene. This alteration results from a G to A substitution at nucleotide position 436, causing the alanine (A) at amino acid position 146 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000638275 SCV002081716 uncertain significance Glycine encephalopathy 2019-10-28 no assertion criteria provided clinical testing

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