TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16407	49444;49445;49446	chr2:178614178;178614177;178614176	chr2:179478905;179478904;179478903
N2AB	14766	44521;44522;44523	chr2:178614178;178614177;178614176	chr2:179478905;179478904;179478903
N2A	13839	41740;41741;41742	chr2:178614178;178614177;178614176	chr2:179478905;179478904;179478903
N2B	7342	22249;22250;22251	chr2:178614178;178614177;178614176	chr2:179478905;179478904;179478903
Novex-1	7467	22624;22625;22626	chr2:178614178;178614177;178614176	chr2:179478905;179478904;179478903
Novex-2	7534	22825;22826;22827	chr2:178614178;178614177;178614176	chr2:179478905;179478904;179478903
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-6
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.7368
• 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
D/Y	None	None	0.989	D	0.441	0.326	0.570648228706	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
D/A	0.1324	likely_benign	0.1244	benign	-0.135	Destabilizing	0.801	D	0.43	neutral	N	0.467444212	None	None	N
D/C	0.6032	likely_pathogenic	0.603	pathogenic	-0.15	Destabilizing	0.998	D	0.449	neutral	None	None	None	None	N
D/E	0.1034	likely_benign	0.0987	benign	-0.378	Destabilizing	0.012	N	0.111	neutral	N	0.445107015	None	None	N
D/F	0.5932	likely_pathogenic	0.5707	pathogenic	0.152	Stabilizing	0.949	D	0.44	neutral	None	None	None	None	N
D/G	0.1196	likely_benign	0.1156	benign	-0.379	Destabilizing	0.891	D	0.42	neutral	N	0.461070529	None	None	N
D/H	0.3013	likely_benign	0.2829	benign	0.409	Stabilizing	0.966	D	0.419	neutral	N	0.479254883	None	None	N
D/I	0.3521	ambiguous	0.34	ambiguous	0.472	Stabilizing	0.904	D	0.425	neutral	None	None	None	None	N
D/K	0.3154	likely_benign	0.2921	benign	0.207	Stabilizing	0.728	D	0.433	neutral	None	None	None	None	N
D/L	0.3635	ambiguous	0.3395	benign	0.472	Stabilizing	0.016	N	0.321	neutral	None	None	None	None	N
D/M	0.5077	ambiguous	0.4846	ambiguous	0.413	Stabilizing	0.949	D	0.429	neutral	None	None	None	None	N
D/N	0.0933	likely_benign	0.0904	benign	-0.243	Destabilizing	0.801	D	0.415	neutral	N	0.479814933	None	None	N
D/P	0.8894	likely_pathogenic	0.8737	pathogenic	0.294	Stabilizing	0.974	D	0.445	neutral	None	None	None	None	N
D/Q	0.26	likely_benign	0.2361	benign	-0.153	Destabilizing	0.172	N	0.109	neutral	None	None	None	None	N
D/R	0.4198	ambiguous	0.3829	ambiguous	0.52	Stabilizing	0.949	D	0.429	neutral	None	None	None	None	N
D/S	0.1157	likely_benign	0.1137	benign	-0.354	Destabilizing	0.842	D	0.347	neutral	None	None	None	None	N
D/T	0.1811	likely_benign	0.1763	benign	-0.153	Destabilizing	0.842	D	0.461	neutral	None	None	None	None	N
D/V	0.1959	likely_benign	0.1941	benign	0.294	Stabilizing	0.669	D	0.452	neutral	N	0.479677753	None	None	N
D/W	0.9027	likely_pathogenic	0.8852	pathogenic	0.302	Stabilizing	0.998	D	0.547	neutral	None	None	None	None	N
D/Y	0.2643	likely_benign	0.2492	benign	0.402	Stabilizing	0.989	D	0.441	neutral	D	0.536942627	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.