Submissions for variant NM_003052.5(SLC34A1):c.782G>A (p.Arg261His)

gnomAD frequency: 0.00066  dbSNP: rs144306414

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000387892	SCV000456676	benign	Hypophosphatemic nephrolithiasis/osteoporosis 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001214517	SCV001386201	uncertain significance	not provided	2022-10-18	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 261 of the SLC34A1 protein (p.Arg261His). This variant is present in population databases (rs144306414, gnomAD 0.07%). This missense change has been observed in individual(s) with hypophosphatemia (PMID: 31672324). ClinVar contains an entry for this variant (Variation ID: 352966). 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 SLC34A1 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.
GeneDx	RCV001214517	SCV002817738	uncertain significance	not provided	2022-06-29	criteria provided, single submitter	clinical testing	Reported as uncertain clinical significance in a patient with renal hypophosphatemia without a second variant identified (Hureaux et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31672324)
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003320634	SCV004025093	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005033888	SCV005671533	uncertain significance	Hypophosphatemic nephrolithiasis/osteoporosis 1; Fanconi renotubular syndrome 2; Hypercalcemia, infantile, 2	2024-02-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530423	SCV004724407	uncertain significance	SLC34A1-related disorder	2023-11-01	no assertion criteria provided	clinical testing	The SLC34A1 c.782G>A variant is predicted to result in the amino acid substitution p.Arg261His. This variant was reported in the heterozygous state in an individual with renal hypophosphatemia (Table S1, Hureaux et al. 2019. PubMed ID: 31672324). This variant is reported in 0.068% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-176815132-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.