ClinVar Miner

Submissions for variant NM_004431.5(EPHA2):c.1118C>T (p.Ser373Phe)

gnomAD frequency: 0.00003  dbSNP: rs758978165
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538935 SCV000644726 uncertain significance Cataract 6 multiple types 2017-07-19 criteria provided, single submitter clinical testing 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with EPHA2-related disease. This variant is present in population databases (rs758978165, ExAC 0.002%). This sequence change replaces serine with phenylalanine at codon 373 of the EPHA2 protein (p.Ser373Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine.
Illumina Laboratory Services, Illumina RCV000538935 SCV001256473 uncertain significance Cataract 6 multiple types 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.
Ambry Genetics RCV004619326 SCV005118906 uncertain significance Inborn genetic diseases 2024-03-18 criteria provided, single submitter clinical testing The c.1118C>T (p.S373F) alteration is located in exon 5 (coding exon 5) of the EPHA2 gene. This alteration results from a C to T substitution at nucleotide position 1118, causing the serine (S) at amino acid position 373 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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