TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16352	49279;49280;49281	chr2:178614343;178614342;178614341	chr2:179479070;179479069;179479068
N2AB	14711	44356;44357;44358	chr2:178614343;178614342;178614341	chr2:179479070;179479069;179479068
N2A	13784	41575;41576;41577	chr2:178614343;178614342;178614341	chr2:179479070;179479069;179479068
N2B	7287	22084;22085;22086	chr2:178614343;178614342;178614341	chr2:179479070;179479069;179479068
Novex-1	7412	22459;22460;22461	chr2:178614343;178614342;178614341	chr2:179479070;179479069;179479068
Novex-2	7479	22660;22661;22662	chr2:178614343;178614342;178614341	chr2:179479070;179479069;179479068
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-6
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1101
• 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
P/T	rs2056897383	None	1.0	D	0.749	0.786	0.759881226992	gnomAD-4.0.0	1.59449E-06	None	None	None	None	N	None	0	2.29253E-05	None	0	0	None	0	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
P/A	0.9335	likely_pathogenic	0.9257	pathogenic	-1.537	Destabilizing	0.999	D	0.788	deleterious	D	0.747739477	None	None	N
P/C	0.9966	likely_pathogenic	0.9958	pathogenic	-1.983	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.332	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/E	0.9991	likely_pathogenic	0.9991	pathogenic	-3.249	Highly Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
P/F	0.9999	likely_pathogenic	0.9998	pathogenic	-0.974	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/G	0.9961	likely_pathogenic	0.9961	pathogenic	-1.879	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/H	0.9993	likely_pathogenic	0.9992	pathogenic	-1.345	Destabilizing	1.0	D	0.812	deleterious	D	0.79963472	None	None	N
P/I	0.9975	likely_pathogenic	0.9969	pathogenic	-0.638	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/K	0.9994	likely_pathogenic	0.9994	pathogenic	-1.488	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
P/L	0.9911	likely_pathogenic	0.9895	pathogenic	-0.638	Destabilizing	1.0	D	0.829	deleterious	D	0.800188701	None	None	N
P/M	0.9988	likely_pathogenic	0.9985	pathogenic	-0.937	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/N	0.9996	likely_pathogenic	0.9996	pathogenic	-1.852	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/Q	0.999	likely_pathogenic	0.9989	pathogenic	-1.954	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/R	0.998	likely_pathogenic	0.9979	pathogenic	-1.086	Destabilizing	1.0	D	0.841	deleterious	D	0.767151014	None	None	N
P/S	0.996	likely_pathogenic	0.9953	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.741	deleterious	D	0.767063914	None	None	N
P/T	0.9941	likely_pathogenic	0.9931	pathogenic	-1.979	Destabilizing	1.0	D	0.749	deleterious	D	0.800188701	None	None	N
P/V	0.9905	likely_pathogenic	0.9889	pathogenic	-0.912	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.365	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9998	pathogenic	-1.042	Destabilizing	1.0	D	0.861	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.