ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.1000T>C (p.Tyr334His)

gnomAD frequency: 0.00006  dbSNP: rs150464408
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502903 SCV000597872 uncertain significance not specified 2016-07-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001205853 SCV001377131 uncertain significance Cohen syndrome 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 334 of the VPS13B protein (p.Tyr334His). This variant is present in population databases (rs150464408, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 437234). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV004023407 SCV004978115 uncertain significance Inborn genetic diseases 2023-12-13 criteria provided, single submitter clinical testing The c.1000T>C (p.Y334H) alteration is located in exon 8 (coding exon 7) of the VPS13B gene. This alteration results from a T to C substitution at nucleotide position 1000, causing the tyrosine (Y) at amino acid position 334 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001205853 SCV002079455 uncertain significance Cohen syndrome 2019-11-11 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004742465 SCV005364618 uncertain significance VPS13B-related disorder 2024-03-07 no assertion criteria provided clinical testing The VPS13B c.1000T>C variant is predicted to result in the amino acid substitution p.Tyr334His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of European (Non-Finnish) descent in gnomAD. 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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