ClinVar Miner

Submissions for variant NM_000343.4(SLC5A1):c.1006C>T (p.Arg336Cys)

dbSNP: rs768831308
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001888691 SCV002153174 uncertain significance Congenital glucose-galactose malabsorption 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 336 of the SLC5A1 protein (p.Arg336Cys). This variant is present in population databases (rs768831308, gnomAD 0.003%). This missense change has been observed in individual(s) with glucose‚Äêgalactose malabsorption (PMID: 30656007). ClinVar contains an entry for this variant (Variation ID: 1381467). 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 expected to disrupt SLC5A1 protein function with a positive predictive value of 80%. 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.
3billion RCV001888691 SCV002521599 likely pathogenic Congenital glucose-galactose malabsorption 2022-05-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.84; 3Cnet: 0.90). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SLC5A1 related disorder (PMID: 30656007). A different missense change at the same codon (p.Arg336His) has been reported to be associated with SLC5A1 related disorder (ClinVar ID: VCV000803682). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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