ClinVar Miner

Submissions for variant NM_000372.5(TYR):c.1366+1G>T

gnomAD frequency: 0.00002  dbSNP: rs369610829
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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 RCV001897211 SCV002157245 pathogenic not provided 2024-02-22 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the TYR gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs369610829, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TYR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1381832). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the TYR protein in which other variant(s) (p.Ala490Cysfs*20) have been determined to be pathogenic (PMID: 1642278, 1711223, 13680365, 18463683, 29345414). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003464201 SCV004207571 likely pathogenic SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2023-09-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005005333 SCV005631394 likely pathogenic Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN 2024-04-22 criteria provided, single submitter clinical testing

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