ClinVar Miner

Submissions for variant NM_030943.4(AMN):c.122C>T (p.Thr41Ile)

gnomAD frequency: 0.00005  dbSNP: rs119478058
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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 RCV001851660 SCV002248376 likely pathogenic Imerslund-Grasbeck syndrome 2024-02-16 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 41 of the AMN protein (p.Thr41Ile). This variant is present in population databases (rs119478058, gnomAD 0.006%). This missense change has been observed in individuals with clinical features of Imerslund-GraÃàsbeck syndrome (PMID: 12590260, 22929189). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4770). 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 AMN protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects AMN function (PMID: 30523278). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000005036 SCV005637451 likely pathogenic Imerslund-Grasbeck syndrome type 2 2024-04-16 criteria provided, single submitter clinical testing
OMIM RCV000005036 SCV000025212 pathogenic Imerslund-Grasbeck syndrome type 2 2003-03-01 no assertion criteria provided literature only

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