Submissions for variant NM_000088.4(COL1A1):c.3278G>A (p.Arg1093His)

gnomAD frequency: 0.00004  dbSNP: rs781491172

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000871482	SCV001013151	benign	Osteogenesis imperfecta type I	2023-04-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001125399	SCV001284461	uncertain significance	Infantile cortical hyperostosis	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	RCV001125400	SCV001284462	likely benign	Osteogenesis imperfecta	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001125401	SCV001284463	likely benign	Ehlers-Danlos syndrome, arthrochalasia type	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Athena Diagnostics	RCV001289259	SCV001476964	uncertain significance	not provided	2020-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001289259	SCV001795762	uncertain significance	not provided	2020-07-06	criteria provided, single submitter	clinical testing	Identified in an individual in published literature (Marshall et al., 2016) with severe antenatal OI, however, this variant was inherited from this individual's unaffected mother, and this individual also harbored a de novo pathogenic variant in the COL1A1 gene thought to explain the patient's phenotype; Identified in three individuals with aortic aneurysm, however, familial segregation information was not included (Weerakkody et al., 2018); 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: 31429852, 29543232, 27549894)
Ambry Genetics	RCV002442860	SCV002612087	likely benign	Cardiovascular phenotype	2022-08-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.