ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.641del (p.Pro214fs) (rs759412460)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668489 SCV000793102 likely pathogenic Familial dysautonomia 2017-07-27 criteria provided, single submitter clinical testing
GeneID Lab - Advanced Molecular Diagnostics RCV000668489 SCV000807810 likely pathogenic Familial dysautonomia 2018-03-10 criteria provided, single submitter clinical testing This variant deletes one nucleotide resulting in an amino acid alteration, replacing a proline (P) with a glutamine (Q) at codon 214 creating a premature stop signal in the new reading frame noted as p.P214Qfs*39. The substitution is predicted to result in a non-functional ELP1 protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), and it has not been reported in the Clinical Variant Database (NCBI National Library of Medicine, NIH) but it has been described in 7 alleles out of 119208, the majority (6) belonging to heterozygous carries of Latino origin. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant.
Invitae RCV000808850 SCV000948974 pathogenic not provided 2018-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro214Glnfs*39) in the ELP1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs759412460, ExAC 0.05%). This variant has not been reported in the literature in individuals with ELP1-related disease. ClinVar contains an entry for this variant (Variation ID: 553108). Loss-of-function variants in ELP1 are known to be pathogenic (PMID: 18303054, 24173031). For these reasons, this variant has been classified as Pathogenic.

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