ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.1189G>T (p.Ala397Ser)

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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 RCV002970825 SCV003279948 uncertain significance Cohen syndrome 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 397 of the VPS13B protein (p.Ala397Ser). This variant is present in population databases (rs763839770, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. 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 expected to disrupt VPS13B protein function. 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.
Ambry Genetics RCV004068153 SCV004978123 uncertain significance Inborn genetic diseases 2023-12-15 criteria provided, single submitter clinical testing The c.1189G>T (p.A397S) alteration is located in exon 8 (coding exon 7) of the VPS13B gene. This alteration results from a G to T substitution at nucleotide position 1189, causing the alanine (A) at amino acid position 397 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004744501 SCV005354363 uncertain significance VPS13B-related disorder 2023-10-27 no assertion criteria provided clinical testing The VPS13B c.1189G>T variant is predicted to result in the amino acid substitution p.Ala397Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-100133656-G-T). 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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