ClinVar Miner

Submissions for variant NM_022787.4(NMNAT1):c.716T>C (p.Leu239Ser)

gnomAD frequency: 0.00001  dbSNP: rs778606847
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538650 SCV000639244 pathogenic Leber congenital amaurosis 9 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 239 of the NMNAT1 protein (p.Leu239Ser). This variant is present in population databases (rs778606847, gnomAD 0.003%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 22842229). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 464670). 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%. Experimental studies have shown that this missense change affects NMNAT1 function (PMID: 26018082). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Genetics in Ophthalmology, Institut Imagine RCV000538650 SCV001433043 pathogenic Leber congenital amaurosis 9 no assertion criteria provided research

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