TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28909	86950;86951;86952	chr2:178559407;178559406;178559405	chr2:179424134;179424133;179424132
N2AB	27268	82027;82028;82029	chr2:178559407;178559406;178559405	chr2:179424134;179424133;179424132
N2A	26341	79246;79247;79248	chr2:178559407;178559406;178559405	chr2:179424134;179424133;179424132
N2B	19844	59755;59756;59757	chr2:178559407;178559406;178559405	chr2:179424134;179424133;179424132
Novex-1	19969	60130;60131;60132	chr2:178559407;178559406;178559405	chr2:179424134;179424133;179424132
Novex-2	20036	60331;60332;60333	chr2:178559407;178559406;178559405	chr2:179424134;179424133;179424132
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-98
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.119
• Predicted PPI site: N

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
L/F	None	None	1.0	D	0.883	0.658	0.802462509306	gnomAD-4.0.0	6.84255E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87266E-05	0	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
L/A	0.9423	likely_pathogenic	0.9534	pathogenic	-2.764	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/C	0.8829	likely_pathogenic	0.9005	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9995	pathogenic	-2.55	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/E	0.9964	likely_pathogenic	0.9973	pathogenic	-2.374	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/F	0.7791	likely_pathogenic	0.811	pathogenic	-1.839	Destabilizing	1.0	D	0.883	deleterious	D	0.650814198	None	None	N
L/G	0.9869	likely_pathogenic	0.991	pathogenic	-3.285	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/H	0.9905	likely_pathogenic	0.9926	pathogenic	-2.465	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/I	0.2855	likely_benign	0.3303	benign	-1.282	Destabilizing	0.969	D	0.852	deleterious	D	0.612426668	None	None	N
L/K	0.9943	likely_pathogenic	0.9961	pathogenic	-2.123	Highly Destabilizing	0.999	D	0.866	deleterious	None	None	None	None	N
L/M	0.3556	ambiguous	0.3982	ambiguous	-1.251	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/N	0.9939	likely_pathogenic	0.9955	pathogenic	-2.332	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/P	0.9925	likely_pathogenic	0.9943	pathogenic	-1.753	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/Q	0.9798	likely_pathogenic	0.9848	pathogenic	-2.295	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/R	0.9866	likely_pathogenic	0.9896	pathogenic	-1.65	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/S	0.9893	likely_pathogenic	0.992	pathogenic	-3.155	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.651621415	None	None	N
L/T	0.94	likely_pathogenic	0.9536	pathogenic	-2.822	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/V	0.3225	likely_benign	0.3653	ambiguous	-1.753	Destabilizing	0.521	D	0.619	neutral	D	0.584909797	None	None	N
L/W	0.9828	likely_pathogenic	0.9855	pathogenic	-2.034	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/Y	0.9849	likely_pathogenic	0.9884	pathogenic	-1.818	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N

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.