ClinVar Miner

Submissions for variant NM_022787.4(NMNAT1):c.634G>A (p.Val212Met)

gnomAD frequency: 0.00004  dbSNP: rs201994921
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001090804 SCV001246534 pathogenic not provided 2020-01-01 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376488 SCV001573654 uncertain significance Leber congenital amaurosis 9 2021-04-08 criteria provided, single submitter research The NMNAT1 c.634G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PM3-S. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Invitae RCV001376488 SCV001588903 pathogenic Leber congenital amaurosis 9 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 212 of the NMNAT1 protein (p.Val212Met). This variant is present in population databases (rs201994921, gnomAD 0.01%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 25412400, 28453600, 29074561). 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: 871051). 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 NMNAT1 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001090804 SCV001826600 likely pathogenic not provided 2020-12-31 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27422788, 27375279, 28453600, 29074561, 25412400, 31054281)
Genomics England Pilot Project, Genomics England RCV001376488 SCV001759973 pathogenic Leber congenital amaurosis 9 no assertion criteria provided clinical testing

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