Submissions for variant NM_000088.4(COL1A1):c.3733A>T (p.Ile1245Phe)

gnomAD frequency: 0.00001  dbSNP: rs199514372

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000319514	SCV000340715	uncertain significance	not provided	2016-05-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001127365	SCV001286672	uncertain significance	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 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	RCV001127366	SCV001286673	uncertain significance	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 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	RCV001127367	SCV001286674	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001296479	SCV001485445	likely benign	Osteogenesis imperfecta type I	2024-11-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000319514	SCV001824237	uncertain significance	not provided	2020-07-28	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 (Stenson et al., 2014); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 287066; Landrum et al., 2016)
Ambry Genetics	RCV002348009	SCV002622523	uncertain significance	Cardiovascular phenotype	2025-02-28	criteria provided, single submitter	clinical testing	The p.I1245F variant (also known as c.3733A>T), located in coding exon 48 of the COL1A1 gene, results from an A to T substitution at nucleotide position 3733. The isoleucine at codon 1245 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is 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	RCV000319514	SCV004224398	uncertain significance	not provided	2023-01-26	criteria provided, single submitter	clinical testing