TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20400	61423;61424;61425	chr2:178590527;178590526;178590525	chr2:179455254;179455253;179455252
N2AB	18759	56500;56501;56502	chr2:178590527;178590526;178590525	chr2:179455254;179455253;179455252
N2A	17832	53719;53720;53721	chr2:178590527;178590526;178590525	chr2:179455254;179455253;179455252
N2B	11335	34228;34229;34230	chr2:178590527;178590526;178590525	chr2:179455254;179455253;179455252
Novex-1	11460	34603;34604;34605	chr2:178590527;178590526;178590525	chr2:179455254;179455253;179455252
Novex-2	11527	34804;34805;34806	chr2:178590527;178590526;178590525	chr2:179455254;179455253;179455252
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-36
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.5827
• 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	0.813	N	0.562	0.451	0.27855597813	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

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	0.9156	likely_pathogenic	0.9303	pathogenic	-0.159	Destabilizing	0.998	D	0.573	neutral	N	0.485176944	None	None	I
G/C	0.9402	likely_pathogenic	0.9575	pathogenic	-0.877	Destabilizing	1.0	D	0.819	deleterious	N	0.510816071	None	None	I
G/D	0.9712	likely_pathogenic	0.9819	pathogenic	-0.471	Destabilizing	0.813	D	0.562	neutral	N	0.492418646	None	None	I
G/E	0.9866	likely_pathogenic	0.9899	pathogenic	-0.631	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	I
G/F	0.9872	likely_pathogenic	0.9917	pathogenic	-0.947	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/H	0.9861	likely_pathogenic	0.9914	pathogenic	-0.28	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/I	0.9881	likely_pathogenic	0.9918	pathogenic	-0.413	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/K	0.9892	likely_pathogenic	0.9923	pathogenic	-0.53	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/L	0.9834	likely_pathogenic	0.9865	pathogenic	-0.413	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/M	0.991	likely_pathogenic	0.9925	pathogenic	-0.513	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/N	0.9635	likely_pathogenic	0.9716	pathogenic	-0.246	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
G/P	0.9979	likely_pathogenic	0.9987	pathogenic	-0.302	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/Q	0.9799	likely_pathogenic	0.9852	pathogenic	-0.514	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/R	0.9702	likely_pathogenic	0.9804	pathogenic	-0.133	Destabilizing	1.0	D	0.81	deleterious	N	0.494406883	None	None	I
G/S	0.8271	likely_pathogenic	0.8655	pathogenic	-0.39	Destabilizing	1.0	D	0.688	prob.neutral	N	0.490937389	None	None	I
G/T	0.9711	likely_pathogenic	0.9774	pathogenic	-0.483	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/V	0.981	likely_pathogenic	0.9864	pathogenic	-0.302	Destabilizing	1.0	D	0.8	deleterious	D	0.532425818	None	None	I
G/W	0.9813	likely_pathogenic	0.9897	pathogenic	-1.057	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/Y	0.9826	likely_pathogenic	0.9888	pathogenic	-0.727	Destabilizing	1.0	D	0.802	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.