Submissions for variant NM_001177316.2(SLC34A3):c.1561dup (p.Leu521fs)

dbSNP: rs765816079

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000513018	SCV000608399	pathogenic	Autosomal recessive hypophosphatemic bone disease	2013-11-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000522409	SCV000620775	likely pathogenic	not provided	2023-05-10	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 79 amino acids are replaced with 71 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24077912, 33532864, 27535533, 32311027)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000522409	SCV001382944	pathogenic	not provided	2024-12-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu521Profs*72) in the SLC34A3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 79 amino acid(s) of the SLC34A3 protein. This variant is present in population databases (rs765816079, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC34A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 444095). This variant disrupts a region of the SLC34A3 protein in which other variant(s) (p.Trp541*) have been determined to be pathogenic (PMID: 31440709). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Molecular Biology Laboratory, Fundació Puigvert	RCV000513018	SCV001425258	pathogenic	Autosomal recessive hypophosphatemic bone disease	2020-02-01	criteria provided, single submitter	research
Fulgent Genetics, Fulgent Genetics	RCV000513018	SCV001752500	pathogenic	Autosomal recessive hypophosphatemic bone disease	2021-11-24	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000513018	SCV002023557	likely pathogenic	Autosomal recessive hypophosphatemic bone disease	2020-07-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003419882	SCV004108484	pathogenic	SLC34A3-related disorder	2022-11-21	criteria provided, single submitter	clinical testing	The SLC34A3 c.1561dupC variant is predicted to result in a frameshift and premature protein termination (p.Leu521Profs*72). This variant was reported in the homozygous state in an individual with hypophosphataemic rickets with hypercalciuria (Domingo-Gallego A et al 2022. PubMed ID: 33532864). This variant was also reported to possibly show digenic inheritance in a family with an additional missense variant in SLC34A1 and varying degrees of hypophosphataemic rickets with hypercalciuria (Gordon et al 2020. PubMed ID: 32311027). This variant is reported in 0.026% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-140130625-T-TC). Frameshift variants in SLC34A3 are expected to be pathogenic. This variant is interpreted as pathogenic.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000522409	SCV005198274	likely pathogenic	not provided	2022-07-13	criteria provided, single submitter	clinical testing