ClinVar Miner

Submissions for variant NM_022787.4(NMNAT1):c.547C>T (p.Leu183Phe)

gnomAD frequency: 0.00001  dbSNP: rs1337014971
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001340858 SCV001534691 likely pathogenic Leber congenital amaurosis 9 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 183 of the NMNAT1 protein (p.Leu183Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with Leber’s congenital amaurosis (PMID: 36140798). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1037668). 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 expected to disrupt NMNAT1 protein function with a positive predictive value of 80%. 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.
Revvity Omics, Revvity RCV003132433 SCV003815963 uncertain significance not provided 2022-03-25 criteria provided, single submitter clinical testing

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