TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8910	26953;26954;26955	chr2:178713930;178713929;178713928	chr2:179578657;179578656;179578655
N2AB	8593	26002;26003;26004	chr2:178713930;178713929;178713928	chr2:179578657;179578656;179578655
N2A	7666	23221;23222;23223	chr2:178713930;178713929;178713928	chr2:179578657;179578656;179578655
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-74
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.7415
• 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
K/Q	rs760765484	0.359	0.051	N	0.205	0.117	0.192905019026	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	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
K/A	0.2353	likely_benign	0.2712	benign	-0.229	Destabilizing	0.842	D	0.529	neutral	None	None	None	None	N
K/C	0.5946	likely_pathogenic	0.6739	pathogenic	-0.33	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
K/D	0.4314	ambiguous	0.4741	ambiguous	-0.013	Destabilizing	0.728	D	0.555	neutral	None	None	None	None	N
K/E	0.1107	likely_benign	0.1145	benign	0.008	Stabilizing	0.012	N	0.241	neutral	N	0.448440792	None	None	N
K/F	0.6018	likely_pathogenic	0.6517	pathogenic	-0.35	Destabilizing	0.991	D	0.626	neutral	None	None	None	None	N
K/G	0.315	likely_benign	0.3673	ambiguous	-0.477	Destabilizing	0.842	D	0.598	neutral	None	None	None	None	N
K/H	0.2431	likely_benign	0.272	benign	-0.846	Destabilizing	0.974	D	0.587	neutral	None	None	None	None	N
K/I	0.2749	likely_benign	0.3011	benign	0.358	Stabilizing	0.934	D	0.623	neutral	N	0.513572493	None	None	N
K/L	0.2886	likely_benign	0.3212	benign	0.358	Stabilizing	0.842	D	0.602	neutral	None	None	None	None	N
K/M	0.167	likely_benign	0.1759	benign	0.341	Stabilizing	0.993	D	0.585	neutral	None	None	None	None	N
K/N	0.2575	likely_benign	0.2851	benign	0.063	Stabilizing	0.801	D	0.517	neutral	N	0.4988724	None	None	N
K/P	0.8321	likely_pathogenic	0.8719	pathogenic	0.192	Stabilizing	0.974	D	0.572	neutral	None	None	None	None	N
K/Q	0.106	likely_benign	0.1126	benign	-0.192	Destabilizing	0.051	N	0.205	neutral	N	0.480342567	None	None	N
K/R	0.078	likely_benign	0.0839	benign	-0.157	Destabilizing	0.669	D	0.507	neutral	N	0.479670563	None	None	N
K/S	0.2281	likely_benign	0.2582	benign	-0.532	Destabilizing	0.728	D	0.467	neutral	None	None	None	None	N
K/T	0.11	likely_benign	0.1185	benign	-0.347	Destabilizing	0.051	N	0.314	neutral	N	0.47841977	None	None	N
K/V	0.2454	likely_benign	0.2765	benign	0.192	Stabilizing	0.842	D	0.573	neutral	None	None	None	None	N
K/W	0.6291	likely_pathogenic	0.6833	pathogenic	-0.248	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
K/Y	0.4926	ambiguous	0.5477	ambiguous	0.088	Stabilizing	0.991	D	0.631	neutral	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.