ClinVar Miner

Submissions for variant NM_001098484.3(SLC4A4):c.1361C>T (p.Ala454Val)

gnomAD frequency: 0.00035  dbSNP: rs138493429
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001153586 SCV001314881 uncertain significance Autosomal recessive proximal renal tubular acidosis 2018-01-12 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV001760109 SCV001999116 uncertain significance not provided 2019-10-15 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001760109 SCV003490579 uncertain significance not provided 2022-11-13 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 905198). This variant has not been reported in the literature in individuals affected with SLC4A4-related conditions. This variant is present in population databases (rs138493429, gnomAD 0.08%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 410 of the SLC4A4 protein (p.Ala410Val). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.
Ambry Genetics RCV002557305 SCV003732998 uncertain significance Inborn genetic diseases 2021-06-17 criteria provided, single submitter clinical testing The c.1229C>T (p.A410V) alteration is located in exon 9 (coding exon 9) of the SLC4A4 gene. This alteration results from a C to T substitution at nucleotide position 1229, causing the alanine (A) at amino acid position 410 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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