Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001387314 | SCV001587914 | pathogenic | not provided | 2023-11-09 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 6 of the SLC34A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC34A1 are known to be pathogenic (PMID: 26047794). This variant is present in population databases (rs201304511, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of infantile hypercalcemia (PMID: 26047794, 28893421, 29959532). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 234926). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003929923 | SCV004738986 | pathogenic | SLC34A1-related condition | 2024-02-15 | criteria provided, single submitter | clinical testing | The SLC34A1 c.644+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in the homozygous and compound heterozygous states in individuals with infantile hypercalcemia (Schlingmann et al 2016. PubMed ID: 26047794; Daga et al 2017. PubMed ID: 28893421; Hureaux et al 2018. PubMed ID: 29959532). This variant is reported in 0.014% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Variants that disrupt consensus splice donor sites in SLC34A1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
OMIM | RCV000223675 | SCV000280015 | pathogenic | Hypercalcemia, infantile, 2 | 2016-10-06 | no assertion criteria provided | literature only | |
Yale Center for Mendelian Genomics, |
RCV000662327 | SCV000784659 | likely pathogenic | Nephrocalcinosis; Nephrolithiasis | 2017-09-08 | no assertion criteria provided | literature only |