ClinVar Miner

Submissions for variant NM_005629.4(SLC6A8):c.421G>A (p.Val141Ile)

gnomAD frequency: 0.00002  dbSNP: rs1557044413
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001247127 SCV001420532 uncertain significance Creatine transporter deficiency 2022-08-12 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 141 of the SLC6A8 protein (p.Val141Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SLC6A8-related conditions. ClinVar contains an entry for this variant (Variation ID: 971362). 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 SLC6A8 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 RCV001545902 SCV001765321 uncertain significance not provided 2021-08-12 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Ambry Genetics RCV002327602 SCV002629026 uncertain significance Inborn genetic diseases 2017-10-20 criteria provided, single submitter clinical testing The p.V141I variant (also known as c.421G>A), located in coding exon 3 of the SLC6A8 gene, results from a G to A substitution at nucleotide position 421. The valine at codon 141 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001835288 SCV002084551 uncertain significance Creatine deficiency syndrome 1 2021-07-01 no assertion criteria provided clinical testing

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