ClinVar Miner

Submissions for variant NM_018993.4(RIN2):c.40C>T (p.Arg14Ter)

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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 RCV003052943 SCV003446779 pathogenic not provided 2023-08-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 2140100). This variant has not been reported in the literature in individuals affected with RIN2-related conditions. This variant is present in population databases (rs777979761, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Arg14*) in the RIN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RIN2 are known to be pathogenic (PMID: 19631308).
PreventionGenetics, part of Exact Sciences RCV003410054 SCV004109478 uncertain significance RIN2-related disorder 2023-07-18 criteria provided, single submitter clinical testing The RIN2 c.187C>T variant is predicted to result in premature protein termination (p.Arg63*). This variant is alternatively described as c.40C>T (p.Arg14*) using the canonical transcript (NM_018993.4). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.018% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-19870285-C-T). Loss-of-function variants downstream of this variant have been associated with autosomal recessive RIN2-related disorders (see for example Basel-Vanagaite L et al 2009. PubMed ID: 19631308). However, to our knowledge, there are no documented causative variants upstream of the c.187C>T (p.Arg63*) variant identified in this individual. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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