TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20598	62017;62018;62019	chr2:178589933;178589932;178589931	chr2:179454660;179454659;179454658
N2AB	18957	57094;57095;57096	chr2:178589933;178589932;178589931	chr2:179454660;179454659;179454658
N2A	18030	54313;54314;54315	chr2:178589933;178589932;178589931	chr2:179454660;179454659;179454658
N2B	11533	34822;34823;34824	chr2:178589933;178589932;178589931	chr2:179454660;179454659;179454658
Novex-1	11658	35197;35198;35199	chr2:178589933;178589932;178589931	chr2:179454660;179454659;179454658
Novex-2	11725	35398;35399;35400	chr2:178589933;178589932;178589931	chr2:179454660;179454659;179454658
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-37
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.5568
• 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
G/D	None	None	1.0	N	0.716	0.511	0.459729313489	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
G/V	None	None	1.0	D	0.805	0.495	0.664811939827	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	6.17284E-04	0	0	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
G/A	0.8982	likely_pathogenic	0.9252	pathogenic	-0.151	Destabilizing	1.0	D	0.625	neutral	N	0.495948409	None	None	I
G/C	0.9498	likely_pathogenic	0.9618	pathogenic	-0.869	Destabilizing	1.0	D	0.803	deleterious	D	0.529007048	None	None	I
G/D	0.9793	likely_pathogenic	0.9859	pathogenic	-0.31	Destabilizing	1.0	D	0.716	prob.delet.	N	0.521409724	None	None	I
G/E	0.9865	likely_pathogenic	0.9913	pathogenic	-0.459	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/F	0.9865	likely_pathogenic	0.99	pathogenic	-0.901	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/H	0.993	likely_pathogenic	0.9951	pathogenic	-0.266	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/I	0.9837	likely_pathogenic	0.9891	pathogenic	-0.407	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
G/K	0.9932	likely_pathogenic	0.9952	pathogenic	-0.41	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/L	0.9858	likely_pathogenic	0.9897	pathogenic	-0.407	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/M	0.9908	likely_pathogenic	0.9936	pathogenic	-0.505	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
G/N	0.9733	likely_pathogenic	0.9824	pathogenic	-0.179	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
G/P	0.9981	likely_pathogenic	0.9987	pathogenic	-0.298	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/Q	0.9868	likely_pathogenic	0.9914	pathogenic	-0.41	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/R	0.9833	likely_pathogenic	0.9881	pathogenic	-0.082	Destabilizing	1.0	D	0.819	deleterious	N	0.501748533	None	None	I
G/S	0.8653	likely_pathogenic	0.9096	pathogenic	-0.344	Destabilizing	1.0	D	0.709	prob.delet.	N	0.487439259	None	None	I
G/T	0.9735	likely_pathogenic	0.9831	pathogenic	-0.424	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/V	0.9769	likely_pathogenic	0.9849	pathogenic	-0.298	Destabilizing	1.0	D	0.805	deleterious	D	0.539513979	None	None	I
G/W	0.9886	likely_pathogenic	0.9904	pathogenic	-1.005	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/Y	0.9853	likely_pathogenic	0.989	pathogenic	-0.685	Destabilizing	1.0	D	0.788	deleterious	None	None	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.