ClinVar Miner

Submissions for variant NM_001854.4(COL11A1):c.965C>T (p.Pro322Leu)

gnomAD frequency: 0.00088  dbSNP: rs183130583
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000179833 SCV000232147 uncertain significance not provided 2015-04-28 criteria provided, single submitter clinical testing
Invitae RCV000179833 SCV001115225 likely benign not provided 2024-01-17 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001102150 SCV001258804 uncertain significance Stickler syndrome type 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV001102151 SCV001258805 uncertain significance Fibrochondrogenesis 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000179833 SCV001874007 uncertain significance not provided 2022-02-28 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Acke et al., 2014; HGMD)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003488432 SCV004240948 likely benign not specified 2023-12-12 criteria provided, single submitter clinical testing Variant summary: COL11A1 c.965C>T (p.Pro322Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 1613352 control chromosomes, predominantly at a frequency of 0.0044 within the Latino subpopulation in the gnomAD database (v4). c.965C>T has been reported in the literature in one individual affected with sensorineural hearing loss (Florentine_2021). The report does not provide unequivocal conclusions about association of the variant with Stickler Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=3) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign.

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