TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23462	70609;70610;70611	chr2:178575748;178575747;178575746	chr2:179440475;179440474;179440473
N2AB	21821	65686;65687;65688	chr2:178575748;178575747;178575746	chr2:179440475;179440474;179440473
N2A	20894	62905;62906;62907	chr2:178575748;178575747;178575746	chr2:179440475;179440474;179440473
N2B	14397	43414;43415;43416	chr2:178575748;178575747;178575746	chr2:179440475;179440474;179440473
Novex-1	14522	43789;43790;43791	chr2:178575748;178575747;178575746	chr2:179440475;179440474;179440473
Novex-2	14589	43990;43991;43992	chr2:178575748;178575747;178575746	chr2:179440475;179440474;179440473
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-58
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.4707
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
D/N	None	None	1.0	N	0.685	0.399	0.502629187243	gnomAD-4.0.0	1.36861E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31895E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
D/A	0.9615	likely_pathogenic	0.9762	pathogenic	-0.526	Destabilizing	1.0	D	0.713	prob.delet.	N	0.502439188	None	None	I
D/C	0.9933	likely_pathogenic	0.9954	pathogenic	-0.024	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
D/E	0.892	likely_pathogenic	0.9117	pathogenic	-0.53	Destabilizing	0.994	D	0.442	neutral	N	0.486941825	None	None	I
D/F	0.9947	likely_pathogenic	0.9971	pathogenic	-0.462	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
D/G	0.9537	likely_pathogenic	0.9719	pathogenic	-0.795	Destabilizing	1.0	D	0.689	prob.neutral	N	0.506758055	None	None	I
D/H	0.9732	likely_pathogenic	0.9829	pathogenic	-0.742	Destabilizing	1.0	D	0.651	neutral	D	0.52525393	None	None	I
D/I	0.9911	likely_pathogenic	0.9951	pathogenic	0.157	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
D/K	0.991	likely_pathogenic	0.9938	pathogenic	-0.006	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
D/L	0.9854	likely_pathogenic	0.9909	pathogenic	0.157	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
D/M	0.9959	likely_pathogenic	0.9978	pathogenic	0.573	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	I
D/N	0.5579	ambiguous	0.6203	pathogenic	-0.349	Destabilizing	1.0	D	0.685	prob.neutral	N	0.481955076	None	None	I
D/P	0.9919	likely_pathogenic	0.9952	pathogenic	-0.047	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	I
D/Q	0.9839	likely_pathogenic	0.9897	pathogenic	-0.273	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
D/R	0.9871	likely_pathogenic	0.9921	pathogenic	0.01	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/S	0.8108	likely_pathogenic	0.8753	pathogenic	-0.506	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
D/T	0.9404	likely_pathogenic	0.961	pathogenic	-0.287	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
D/V	0.9767	likely_pathogenic	0.9858	pathogenic	-0.047	Destabilizing	1.0	D	0.696	prob.neutral	N	0.513226062	None	None	I
D/W	0.9986	likely_pathogenic	0.9992	pathogenic	-0.324	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
D/Y	0.9606	likely_pathogenic	0.9761	pathogenic	-0.229	Destabilizing	1.0	D	0.631	neutral	D	0.552512445	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.