ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.2681T>G (p.Val894Gly) (rs145137472)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001027802 SCV000396859 uncertain significance Fanconi anemia, complementation group P 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.
Invitae RCV000362095 SCV000626412 uncertain significance Fanconi anemia 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 894 of the SLX4 protein (p.Val894Gly). The valine residue is weakly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is present in population databases (rs145137472, ExAC 0.04%). This variant has not been reported in the literature in individuals with SLX4-related disease. ClinVar contains an entry for this variant (Variation ID: 319164). 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 glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000762181 SCV000892449 uncertain significance not provided 2018-07-01 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001027802 SCV001190415 uncertain significance Fanconi anemia, complementation group P 2019-04-29 criteria provided, single submitter clinical testing SLX4 NM_032444.3 exon 12 p.Val894Gly (c.2681T>G): This variant has not been reported in the literature and is present in 0.1% (11/10370) of Ashkenazi Jewish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-3640958-A-C). This variant is present in ClinVar (Variation ID:319164). This variant amino acid Glycine (Gly) is present in multiple mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Leiden Open Variation Database RCV001194828 SCV001364633 likely benign not specified 2012-08-31 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker.

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