Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001362628 | SCV001558658 | uncertain significance | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 575 of the SLC34A1 protein (p.Thr575Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs201331677, ExAC 0.005%). This missense change has been observed in individuals with SLC34A1-related conditions (PMID: 28893421; Invitae). ClinVar contains an entry for this variant (Variation ID: 548679). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Revvity Omics, |
RCV001362628 | SCV003825679 | uncertain significance | not provided | 2020-12-10 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003420160 | SCV004118455 | uncertain significance | SLC34A1-related condition | 2023-07-20 | criteria provided, single submitter | clinical testing | The SLC34A1 c.1724C>T variant is predicted to result in the amino acid substitution p.Thr575Ile. This variant was reported in the homozygous state in an individual with nephrocalcinosis and hypercalcemia (Daga et al 2018. PubMed ID: 28893421). It was also reported in the heterozygous state in two additional patients from a large exome sequencing cohort; however, clinical information was not provided (Supp. Table 1 in Capalbo A et al 2019. PubMed ID: 31589614). This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-176825091-C-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Yale Center for Mendelian Genomics, |
RCV000662329 | SCV000784661 | likely pathogenic | Nephrocalcinosis; Nephrolithiasis | 2017-09-08 | no assertion criteria provided | literature only |