ClinVar Miner

Submissions for variant NM_001854.4(COL11A1):c.4660dup (p.Thr1554fs) (rs1570630126)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001009029 SCV001168839 likely pathogenic not provided 2018-09-18 criteria provided, single submitter clinical testing Although the c.4660dupA likely pathogenic variant in the COL11A1 gene has not been published to our knowledge, it causes a shift in reading frame starting at threonine 1554, changing it to an asparagine, and creating a premature stop codon at position 6 of the new reading frame, denoted p.T1554NfsX6. This likely pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Furthermore, c.4660dupA has not been observed in large population cohorts (Lek et al., 2016). Loss of function (nonsense and frameshift) variants in the COL11A1 gene have been reported in association with autosomal dominant Stickler or Marshall syndromes (Acke et al., 2014); however, most variants reported to date in the COL11A1 gene in association with these disorders are missense or splice site variants (Stenson et al., 2014). Loss of function variants in the COL11A1 gene have also been reported in individuals with autosomal recessive fibrochondrogenesis in either the homozygous state or a compound heterozygous state with a second protein-altering variant (Tompson et al., 2010; Akawi et al., 2012; Richards et al., 2013). In several families, the parent heterozygous for the loss of function variant manifested milder features, such as hearing loss, not sufficient to establish a clinical diagnosis of Stickler syndrome (Tompson et al., 2010; Richards et al., 2013). In summary, c.4660dupA in the COL11A1 gene is interpreted as a likely pathogenic variant.

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