ClinVar Miner

Submissions for variant NM_018389.5(SLC35C1):c.29G>A (p.Arg10Lys)

gnomAD frequency: 0.00004  dbSNP: rs567155861
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV000279679 SCV005328595 likely benign Leukocyte adhesion deficiency type II 2024-09-20 criteria provided, single submitter clinical testing The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.
Ambry Genetics RCV002520720 SCV003706477 uncertain significance Inborn genetic diseases 2022-05-20 criteria provided, single submitter clinical testing The c.29G>A (p.R10K) alteration is located in exon 1 (coding exon 1) of the SLC35C1 gene. This alteration results from a G to A substitution at nucleotide position 29, causing the arginine (R) at amino acid position 10 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000279679 SCV002812915 uncertain significance Leukocyte adhesion deficiency type II 2021-09-03 criteria provided, single submitter clinical testing
Baylor Genetics RCV000279679 SCV001520383 uncertain significance Leukocyte adhesion deficiency type II 2020-03-05 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV000279679 SCV001376009 uncertain significance Leukocyte adhesion deficiency type II 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 10 of the SLC35C1 protein (p.Arg10Lys). This variant is present in population databases (rs567155861, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC35C1-related conditions. ClinVar contains an entry for this variant (Variation ID: 304736). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV000658193 SCV000779964 uncertain significance not provided 2018-05-29 criteria provided, single submitter clinical testing The R10K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R10K variant is observed in 4/34,418 (0.01%) alleles from individuals of Latino background, in the ExAC dataset (Lek et al., 2016). The R10K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Laboratory Services, Illumina RCV000279679 SCV000372002 uncertain significance Leukocyte adhesion deficiency type II 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, 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.

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