ClinVar Miner

Submissions for variant NM_001854.4(COL11A1):c.4526A>C (p.Gln1509Pro)

gnomAD frequency: 0.00001  dbSNP: rs1057521422
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000444944 SCV000522723 uncertain significance not provided 2024-10-21 criteria provided, single submitter clinical testing Reported in a patient with osteoporosis in published literature (PMID: 30919572); Identified in a patient with bilateral sensorineural hearing loss in published literature who also harbored variants of uncertain significance in other genes associated with hearing loss (PMID: 38378725); Not observed at significant frequency in large population cohorts (gnomAD); Observed in multiple heterozygous individuals and one homozygous individual from a Qatari Biobank cohort, however clinical information was not provided (PMID: 36777185); In silico analysis indicates that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease; This variant is associated with the following publications: (PMID: 38378725, 30919572, 36777185)
Baylor Genetics RCV001330657 SCV001522405 uncertain significance Stickler syndrome type 2 2019-11-07 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV000444944 SCV002276580 uncertain significance not provided 2022-09-09 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL11A1 protein function. ClinVar contains an entry for this variant (Variation ID: 382691). This missense change has been observed in individual(s) with clinical features of COL11A1-related conditions (PMID: 30919572). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1509 of the COL11A1 protein (p.Gln1509Pro).

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