ClinVar Miner

Submissions for variant NM_001101426.4(CRPPA):c.53dup (p.Ser19Glufs) (rs886041302)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000274875 SCV000862104 pathogenic not provided 2018-06-25 criteria provided, single submitter clinical testing
GeneDx RCV000274875 SCV000329669 pathogenic not provided 2018-05-09 criteria provided, single submitter clinical testing The c.53dupT pathogenic variant in the ISPD gene has been previously reported in individuals with ISPD-related disorders who harbor an additional ISPD variant (Roscioli et al., 2012; Cirak et al., 2013). The c.53dupT variant causes a frameshift starting with codon Serine 19, changes this amino acid to a Glutamic acid residue and creates a premature Stop codon at position 97 of the new reading frame, denoted p.Ser19GlufsX97. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.53dupT variant is not observed at a significant frequency in individuals undergoing testing at GeneDx. Therefore, we interpret c.53dupT as a pathogenic variant.
Invitae RCV000650388 SCV000772232 pathogenic Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A7; Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 7 2018-10-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser19Glufs*97) in the ISPD gene. It is expected to result in an absent or disrupted protein product. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported as heterozygous along with a second rare ISPD variant in an individual affected with Walker-Warburg syndrome (PMID: 22522421) and in an individual affected with autosomal recessive limb girdle muscular dystrophy with intellectual disability (PMID: 2328832). ClinVar contains an entry for this variant (Variation ID: 279985). Loss-of-function variants in ISPD are known to be pathogenic (PMID: 23288328). For these reasons, this variant has been classified as Pathogenic.

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