TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19454	58585;58586;58587	chr2:178594033;178594032;178594031	chr2:179458760;179458759;179458758
N2AB	17813	53662;53663;53664	chr2:178594033;178594032;178594031	chr2:179458760;179458759;179458758
N2A	16886	50881;50882;50883	chr2:178594033;178594032;178594031	chr2:179458760;179458759;179458758
N2B	10389	31390;31391;31392	chr2:178594033;178594032;178594031	chr2:179458760;179458759;179458758
Novex-1	10514	31765;31766;31767	chr2:178594033;178594032;178594031	chr2:179458760;179458759;179458758
Novex-2	10581	31966;31967;31968	chr2:178594033;178594032;178594031	chr2:179458760;179458759;179458758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-118
• Domain position: 64
• Structural Position: 151
• Q(SASA): 0.2127
• 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
S/P	None	None	0.991	D	0.795	0.629	0.382761230579	gnomAD-4.0.0	1.59175E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85907E-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
S/A	0.1069	likely_benign	0.1074	benign	-0.883	Destabilizing	0.76	D	0.399	neutral	N	0.482092006	None	None	N
S/C	0.1497	likely_benign	0.1474	benign	-0.768	Destabilizing	0.999	D	0.78	deleterious	N	0.515450194	None	None	N
S/D	0.7843	likely_pathogenic	0.744	pathogenic	-0.771	Destabilizing	0.953	D	0.518	neutral	None	None	None	None	N
S/E	0.8231	likely_pathogenic	0.7964	pathogenic	-0.769	Destabilizing	0.953	D	0.515	neutral	None	None	None	None	N
S/F	0.537	ambiguous	0.5112	ambiguous	-1.284	Destabilizing	0.991	D	0.859	deleterious	D	0.52655301	None	None	N
S/G	0.0992	likely_benign	0.0932	benign	-1.102	Destabilizing	0.953	D	0.447	neutral	None	None	None	None	N
S/H	0.6168	likely_pathogenic	0.5973	pathogenic	-1.604	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
S/I	0.485	ambiguous	0.4745	ambiguous	-0.402	Destabilizing	0.986	D	0.825	deleterious	None	None	None	None	N
S/K	0.8477	likely_pathogenic	0.8246	pathogenic	-0.698	Destabilizing	0.953	D	0.516	neutral	None	None	None	None	N
S/L	0.2611	likely_benign	0.2504	benign	-0.402	Destabilizing	0.91	D	0.637	neutral	None	None	None	None	N
S/M	0.3645	ambiguous	0.3533	ambiguous	0.027	Stabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
S/N	0.3271	likely_benign	0.3122	benign	-0.808	Destabilizing	0.953	D	0.52	neutral	None	None	None	None	N
S/P	0.9287	likely_pathogenic	0.9124	pathogenic	-0.531	Destabilizing	0.991	D	0.795	deleterious	D	0.53782041	None	None	N
S/Q	0.7154	likely_pathogenic	0.7002	pathogenic	-1.042	Destabilizing	0.993	D	0.702	prob.neutral	None	None	None	None	N
S/R	0.7315	likely_pathogenic	0.6898	pathogenic	-0.529	Destabilizing	0.986	D	0.805	deleterious	None	None	None	None	N
S/T	0.0955	likely_benign	0.0872	benign	-0.801	Destabilizing	0.046	N	0.371	neutral	N	0.520919753	None	None	N
S/V	0.4543	ambiguous	0.4419	ambiguous	-0.531	Destabilizing	0.973	D	0.721	prob.delet.	None	None	None	None	N
S/W	0.7089	likely_pathogenic	0.6895	pathogenic	-1.238	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
S/Y	0.5086	ambiguous	0.4848	ambiguous	-0.945	Destabilizing	0.997	D	0.851	deleterious	D	0.538073899	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.