Submissions for variant NM_000088.4(COL1A1):c.3247G>A (p.Ala1083Thr)

gnomAD frequency: 0.00004  dbSNP: rs372029024

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001127481	SCV001286796	uncertain significance	Ehlers-Danlos syndrome, arthrochalasia type	2017-04-28	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	RCV001127482	SCV001286797	uncertain significance	Osteogenesis imperfecta	2017-04-28	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	RCV001127483	SCV001286798	uncertain significance	Infantile cortical hyperostosis	2017-04-28	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001219328	SCV001391262	likely benign	Osteogenesis imperfecta type I	2024-12-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003380850	SCV004088682	uncertain significance	Cardiovascular phenotype	2023-07-25	criteria provided, single submitter	clinical testing	The p.A1083T variant (also known as c.3247G>A), located in coding exon 44 of the COL1A1 gene, results from a G to A substitution at nucleotide position 3247. The alanine at codon 1083 is replaced by threonine, an amino acid with similar properties. This alteration has been reported as compound heterozygous with an additional alteration in COL1A1 in an individual with osteogenesis imperfecta (OI) and was inherited from the unaffected mother (Ju M et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2016 Apr;33:140-4). Additionally, this alteration has been reported in an individual with primary congenital glaucoma; however, additional alterations in other related genes were identified (Mauri L et al. Orphanet J Rare Dis, 2016 Aug;11:108). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV003480969	SCV004224402	uncertain significance	not provided	2023-03-31	criteria provided, single submitter	clinical testing	BP5, PP2