Submissions for variant NM_024598.4(USB1):c.253G>A (p.Val85Ile)

gnomAD frequency: 0.00002  dbSNP: rs764580227

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV001329352	SCV001520771	uncertain significance	Poikiloderma with neutropenia	2019-12-07	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV001751640	SCV001995951	uncertain significance	not provided	2019-09-10	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV001751640	SCV002164777	uncertain significance	not provided	2022-09-16	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 85 of the USB1 protein (p.Val85Ile). This variant is present in population databases (rs764580227, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with USB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1028327). 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 not expected to disrupt USB1 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV001751640	SCV004227594	uncertain significance	not provided	2022-05-11	criteria provided, single submitter	clinical testing	BP4
Ambry Genetics	RCV004968041	SCV005530802	uncertain significance	Inborn genetic diseases	2024-12-04	criteria provided, single submitter	clinical testing	The p.V85I variant (also known as c.253G>A), located in coding exon 2 of the USB1 gene, results from a G to A substitution at nucleotide position 253. The valine at codon 85 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.