ClinVar Miner

Submissions for variant NM_014254.3(RXYLT1):c.123_150del (p.Leu43fs) (rs748590408)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521645 SCV000620932 likely pathogenic not provided 2017-09-26 criteria provided, single submitter clinical testing The c.123_150del28 variant in the TMEM5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.123_150del28 variant causes a frameshift starting with codon Leucine 43, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 37 of the new reading frame, denoted p.Leu43ArgfsX37. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.123_150del28 variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.123_150del28 as a likely pathogenic variant.
Invitae RCV000696278 SCV000824830 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 2017-09-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu43Argfs*37) in the TMEM5 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with TMEM5-related disease. Loss-of-function variants in TMEM5 are known to be pathogenic (PMID: 23217329, 23519211). For these reasons, this variant has been classified as Pathogenic.

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