ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.1799C>T (p.Pro600Leu)

dbSNP: rs749277750
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta RCV000856627 SCV000996527 uncertain significance Fanconi anemia complementation group P 2019-10-18 criteria provided, single submitter clinical testing The Pro600Leu variant has been reported in the heterozygous state in a single individual, who was a part of an aplastic anemia cohort. (Collopy et al.2014) This variant has not been seen in the Human Gene Mutation Database (HGMD) or the Exome Aggregate Consortium (ExAC). The physiochemical difference between Pro and Leu as measured by Grantham's Distance is 98. This score is considered a moderate change (PubMed: 4843792, 6442359). Predictive algorithms: 0/10 deleterious; 10/10 tolerated (AGVGD, FATHMM, FATHMMMKL, LRT, METALR, METASVM, MUTATIONASSESSOR, MUTATIONTASTER, PROVEAN, SIFT).
Invitae RCV001295963 SCV001484916 uncertain significance Fanconi anemia 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 600 of the SLX4 protein (p.Pro600Leu). 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 missense change has been observed in individual(s) with aplastic anemia (PMID: 24763404). ClinVar contains an entry for this variant (Variation ID: 694611). 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 leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Fulgent Genetics, Fulgent Genetics RCV000856627 SCV002791374 uncertain significance Fanconi anemia complementation group P 2022-02-04 criteria provided, single submitter clinical testing

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