ClinVar Miner

Submissions for variant NM_024570.4(RNASEH2B):c.659T>C (p.Ile220Thr)

gnomAD frequency: 0.00001  dbSNP: rs747995413
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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 RCV000823496 SCV000964357 uncertain significance Aicardi-Goutieres syndrome 2 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 220 of the RNASEH2B protein (p.Ile220Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs747995413, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with RNASEH2B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
GeneDx RCV004800607 SCV005421493 likely pathogenic not provided 2024-06-05 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD)
Ambry Genetics RCV004958178 SCV005485688 uncertain significance Inborn genetic diseases 2024-07-05 criteria provided, single submitter clinical testing The c.659T>C (p.I220T) alteration is located in exon 8 (coding exon 8) of the RNASEH2B gene. This alteration results from a T to C substitution at nucleotide position 659, causing the isoleucine (I) at amino acid position 220 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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