Submissions for variant NM_001844.5(COL2A1):c.1300C>T (p.Pro434Ser)

gnomAD frequency: 0.00053  dbSNP: rs140985224

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000723634	SCV000574387	likely benign	not provided	2020-10-21	criteria provided, single submitter	clinical testing	Reported in a French proband with Kniest dysplasia, but was subsequently found to be inherited from an asymptomatic father (Barat-Houari et al., 2016c); Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat and may have an effect on normal protein folding and function, though missense substitution at the Y position is not a common mechanism of disease (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26626311)
Eurofins Ntd Llc (ga)	RCV000723634	SCV000700590	uncertain significance	not provided	2017-03-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001110199	SCV001267603	uncertain significance	Stickler syndrome type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001110200	SCV001267604	benign	Type II Collagenopathies	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center	RCV001375461	SCV001572134	benign	Hearing impairment	2021-04-12	criteria provided, single submitter	clinical testing	PS1_Moderate, PP3_Supporting, BS1_Strong, BS2_Strong
Labcorp Genetics (formerly Invitae), Labcorp	RCV000723634	SCV001693500	likely benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000723634	SCV002050201	likely benign	not provided	2020-12-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000723634	SCV004130673	benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	COL2A1: PP2, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV004535536	SCV004735752	likely benign	COL2A1-related disorder	2021-09-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).