ClinVar Miner

Submissions for variant NM_016366.3(CABP2):c.590T>C (p.Ile197Thr)

gnomAD frequency: 0.00068  dbSNP: rs145369252
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825873 SCV000967358 uncertain significance not specified 2018-09-13 criteria provided, single submitter clinical testing The p.Ile197Thr variant in CABP2 has been reported in the homozygous state in 1 individual with hearing loss (Sloan-Heggen 2015). It has also been identified in 0.05% (66/126628) of European chromosomes by the Genome Aggregation Database (g nomAD, http://gnomad.broadinstitute.org/). Computational prediction tools and co nservation analysis do not provide strong support for or against an impact to th e protein. In summary, the clinical significance of the p.Ile197Thr variant is u ncertain. ACMG/AMP Criteria applied: PM3_Supporting, PM2_Supporting.
GeneDx RCV001796259 SCV002032561 uncertain significance not provided 2024-11-06 criteria provided, single submitter clinical testing Observed in apparent homozygous state in several unrelated patients with hearing loss referred for genetic testing at GeneDx and in published literature; however, also observed in several homozygous clinically unaffected adult relatives of individuals referred for genetic testing at GeneDx (PMID: 38192829); Identified in association with nonsyndromic hearing loss in an additional publication, however, no patient-specific information is available (PMID: 26445815); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 38192829, 26445815)
Labcorp Genetics (formerly Invitae), Labcorp RCV001796259 SCV002141115 pathogenic not provided 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 197 of the CABP2 protein (p.Ile197Thr). This variant is present in population databases (rs145369252, gnomAD 0.05%). This missense change has been observed in individual(s) with nonsyndromic deafness (PMID: 26445815; external communication, internal data). 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: 667198). 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 disruptive. For these reasons, this variant has been classified as Pathogenic.
Daryl Scott Lab, Baylor College of Medicine RCV003396462 SCV004102663 uncertain significance Autosomal recessive nonsyndromic hearing loss 93 2023-11-10 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Ulm RCV003396462 SCV004171029 likely pathogenic Autosomal recessive nonsyndromic hearing loss 93 2020-02-13 no assertion criteria provided research

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