Submissions for variant NM_000342.4(SLC4A1):c.2701C>T (p.Arg901Trp)

gnomAD frequency: 0.00031  dbSNP: rs201265160

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000346002	SCV000403222	benign	Autosomal dominant distal 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 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.
Illumina Laboratory Services, Illumina	RCV000391446	SCV000403223	uncertain significance	Hemolytic anemia	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.
Illumina Laboratory Services, Illumina	RCV000306677	SCV000403224	uncertain significance	Hereditary spherocytosis type 4	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.
CeGaT Center for Human Genetics Tuebingen	RCV000054610	SCV001151342	uncertain significance	not provided	2023-03-01	criteria provided, single submitter	clinical testing	SLC4A1: PM2:Supporting, BP4
Labcorp Genetics (formerly Invitae), Labcorp	RCV000054610	SCV001511630	uncertain significance	not provided	2025-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 901 of the SLC4A1 protein (p.Arg901Trp). This variant is present in population databases (rs201265160, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SLC4A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 64423). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SLC4A1 protein function with a negative 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000054610	SCV001713721	uncertain significance	not provided	2020-10-27	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000054610	SCV004237350	uncertain significance	not provided	2023-07-11	criteria provided, single submitter	clinical testing
Martin Pollak Laboratory, Beth Israel Deaconess Medical Center	RCV000054610	SCV000077300	unknown	not provided		no assertion criteria provided	not provided	Converted during submission to Uncertain significance.