ClinVar Miner

Submissions for variant NM_000883.4(IMPDH1):c.1030C>T (p.Arg344Cys)

gnomAD frequency: 0.00013  dbSNP: rs370988040
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521610 SCV000618576 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing The R344C variant has been reported previously as a benign variant in an individual with retinitis pigmentosa who harbored a homozygous canonical splice variant in ARL6, but additional evidence is not available (Neveling et al., 2012). The R344C variant is observed in 12/65218 (0.018%) alleles from individuals of non-Finnish European background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R344C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (R344H, reported as R308H) has been reported in association with retinitis pigmentosa (Jin et al., 2008), supporting the functional importance of this region of the protein. We interpret R344C as a variant of uncertain significance.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001196203 SCV001366744 uncertain significance Leber congenital amaurosis 11 2019-08-19 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
Labcorp Genetics (formerly Invitae), Labcorp RCV000521610 SCV001375124 uncertain significance not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 344 of the IMPDH1 protein (p.Arg344Cys). This variant is present in population databases (rs370988040, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with IMPDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 450043). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Breakthrough Genomics, Breakthrough Genomics RCV000521610 SCV005195642 uncertain significance not provided criteria provided, single submitter not provided

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