Submissions for variant NM_001854.4(COL11A1):c.2735C>T (p.Pro912Leu)

gnomAD frequency: 0.00009  dbSNP: rs192842970

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001101958	SCV001258602	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001101959	SCV001258603	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	RCV001664688	SCV001872621	uncertain significance	not provided	2023-07-14	criteria provided, single submitter	clinical testing	Identified in a patient referred for genetic testing for hearing loss, reported as p.P924L using alternate nomenclature (Miyagawa et al., 2013); however, additional clinical information was not provided; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23967202)
3billion	RCV001101959	SCV002014715	uncertain significance	Fibrochondrogenesis 1	2021-10-25	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0002, PM2). it has been reported as uncertain significance or likley benign (ClinVar ID: VCV000876781.3) Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Invitae	RCV001664688	SCV002362799	likely benign	not provided	2023-12-18	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001664688	SCV003831144	uncertain significance	not provided	2022-07-26	criteria provided, single submitter	clinical testing