TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29059	87400;87401;87402	chr2:178558179;178558178;178558177	chr2:179422906;179422905;179422904
N2AB	27418	82477;82478;82479	chr2:178558179;178558178;178558177	chr2:179422906;179422905;179422904
N2A	26491	79696;79697;79698	chr2:178558179;178558178;178558177	chr2:179422906;179422905;179422904
N2B	19994	60205;60206;60207	chr2:178558179;178558178;178558177	chr2:179422906;179422905;179422904
Novex-1	20119	60580;60581;60582	chr2:178558179;178558178;178558177	chr2:179422906;179422905;179422904
Novex-2	20186	60781;60782;60783	chr2:178558179;178558178;178558177	chr2:179422906;179422905;179422904
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: Ig-145
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3378
• 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	D	0.883	0.642	0.742091629371	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	0.4161	ambiguous	0.5229	ambiguous	-0.351	Destabilizing	0.974	D	0.493	neutral	D	0.598287855	None	None	I
G/C	0.5134	ambiguous	0.6267	pathogenic	-0.904	Destabilizing	1.0	D	0.825	deleterious	D	0.598893268	None	None	I
G/D	0.5442	ambiguous	0.6827	pathogenic	-0.679	Destabilizing	1.0	D	0.883	deleterious	D	0.580421896	None	None	I
G/E	0.6565	likely_pathogenic	0.788	pathogenic	-0.849	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/F	0.8692	likely_pathogenic	0.9237	pathogenic	-1.135	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/H	0.6545	likely_pathogenic	0.7775	pathogenic	-0.548	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/I	0.8808	likely_pathogenic	0.9349	pathogenic	-0.529	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/K	0.6753	likely_pathogenic	0.8133	pathogenic	-0.73	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/L	0.8189	likely_pathogenic	0.8933	pathogenic	-0.529	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/M	0.8496	likely_pathogenic	0.9153	pathogenic	-0.421	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/N	0.4732	ambiguous	0.6089	pathogenic	-0.438	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/P	0.9842	likely_pathogenic	0.9912	pathogenic	-0.438	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/Q	0.5934	likely_pathogenic	0.7216	pathogenic	-0.77	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
G/R	0.5445	ambiguous	0.6799	pathogenic	-0.264	Destabilizing	1.0	D	0.86	deleterious	D	0.572951548	None	None	I
G/S	0.2341	likely_benign	0.2974	benign	-0.576	Destabilizing	1.0	D	0.835	deleterious	D	0.598086051	None	None	I
G/T	0.5811	likely_pathogenic	0.7083	pathogenic	-0.682	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/V	0.7756	likely_pathogenic	0.8674	pathogenic	-0.438	Destabilizing	1.0	D	0.851	deleterious	D	0.598691464	None	None	I
G/W	0.7909	likely_pathogenic	0.8574	pathogenic	-1.246	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/Y	0.7823	likely_pathogenic	0.8567	pathogenic	-0.904	Destabilizing	1.0	D	0.864	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.