Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414254 | SCV000490787 | likely pathogenic | not provided | 2015-09-25 | criteria provided, single submitter | clinical testing | To our knowledge, the V130M missense change has not been published as a pathogenic variant, nor as a benign polymorphism. However, another missense change located at the same position, V130L, has been reported in association with Shwachman-Diamond syndrome (SDS) (Hashmi et al., 2011). The NHLBI Exome Sequencing Project reports V130M wasobserved in 1/8600 (0.012%) alleles from individuals of European background and the 1000 Genomes ProjectConsortium reports V130M was observed in 1/1008 (0.10%) alleles from individuals of East Asianbackground, indicating it may be a rare variant in these populations. The V130M variant is a conservativeamino acid substitution that occurs at a position that is conserved across species. In silico analysis isinconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Missense variants in nearby residues (N121T, R126T, T129A, M137T) have been reported in the HumanGene Mutation Database in association with Schwachman-Diamond syndrome (Stenson et al., 2014).Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is abenign variant cannot be excluded. |
| Mendelics | RCV000987894 | SCV001137384 | likely pathogenic | Shwachman-Diamond syndrome 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV000987894 | SCV004175813 | likely pathogenic | Shwachman-Diamond syndrome 1 | 2023-02-14 | criteria provided, single submitter | clinical testing | The missense variant c.388G>A (p.Val130Met) in the SBDS gene has been reported previously in a heterozygous state in patients affected with neuroblastoma (Wu et al., 2022; Bonfiglio et al., 2023). This variant is reported with the allele frequency (0.008%) in the gnomAD Exomes and novel (not in any individuals) in 1000 Genomes. It is submitted to ClinVar as Likely Pathogenic. The amino acid Valine at position 130 is changed to a Methionine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted as damaging by SIFT. The amino acid change p.Val130Met in SBDS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. |
| Mayo Clinic Laboratories, |
RCV000414254 | SCV004224019 | uncertain significance | not provided | 2023-01-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004022157 | SCV004943372 | uncertain significance | Inborn genetic diseases | 2022-06-10 | criteria provided, single submitter | clinical testing | The c.388G>A (p.V130M) alteration is located in exon 3 (coding exon 3) of the SBDS gene. This alteration results from a G to A substitution at nucleotide position 388, causing the valine (V) at amino acid position 130 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |