ClinVar Miner

Submissions for variant NM_001854.4(COL11A1):c.3136G>A (p.Gly1046Arg)

gnomAD frequency: 0.00006  dbSNP: rs760387652
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001357013 SCV001789208 uncertain significance not provided 2024-09-17 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; This variant is associated with the following publications: (PMID: 31871067)
Labcorp Genetics (formerly Invitae), Labcorp RCV001357013 SCV002153807 benign not provided 2023-09-24 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001357013 SCV004124129 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV004034476 SCV004929392 uncertain significance Inborn genetic diseases 2021-11-08 criteria provided, single submitter clinical testing The c.3136G>A (p.G1046R) alteration is located in exon 41 (coding exon 41) of the COL11A1 gene. This alteration results from a G to A substitution at nucleotide position 3136, causing the glycine (G) at amino acid position 1046 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357013 SCV001552336 uncertain significance not provided no assertion criteria provided clinical testing The COL11A1 p.Gly1046Arg variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs760387652) and in Cosmic with a FATHMM prediction of pathogenic (score=0.97). The variant was identified in control databases in 9 of 281238 chromosomes at a frequency of 0.000032 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 7156 chromosomes (freq: 0.00014), South Asian in 2 of 30418 chromosomes (freq: 0.000066) and European (non-Finnish) in 6 of 128346 chromosomes (freq: 0.000047); it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, and European (Finnish) populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Gly1046 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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