Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000210539 | SCV000262883 | pathogenic | Inborn genetic diseases | 2014-07-07 | criteria provided, single submitter | clinical testing | The c.3935C>A (p.S1312*) alteration, located in exon 21 (coding exon 20) of the ZFYVE26 gene, consists of a C to A substitution at nucleotide position 3935. This changes the amino acid from a serine (S) to a stop codon at amino acid position 1312. Premature stop codons are typically deleterious in nature (Richards, 2015). Based on data from the NHLBI Exome Sequencing Project (ESP), the c.3935C>A alteration was not observed among 6,503 individuals tested (0.0%). Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project and the alteration is not currently listed in the Database of Single Nucleotide Polymorphisms (dbSNP). Though some variants may appear to be rare due to database-specific ethnic underrepresentation, rare missense alleles commonly exhibit a deleterious effect on protein function (Kryukov, 2007; Tennessen, 2012). IF USED, PULL THESE INTO REFERENCES: Kryukov GV, et al. (2007) Am J Hum Genet 80:727-739. Tennessen JA, et al. (2012) Science 337(64):64-69. Based on the available evidence, this alteration is classified as pathogenic. |
Invitae | RCV001385536 | SCV001585421 | pathogenic | Spastic paraplegia | 2023-08-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 225014). This premature translational stop signal has been observed in individuals with hereditary spastic paraplegia (PMID: 24030950, 24833714). This variant is present in population databases (rs752283089, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Ser1312*) in the ZFYVE26 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZFYVE26 are known to be pathogenic (PMID: 18394578, 19805727). |