TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16313	49162;49163;49164	chr2:178614577;178614576;178614575	chr2:179479304;179479303;179479302
N2AB	14672	44239;44240;44241	chr2:178614577;178614576;178614575	chr2:179479304;179479303;179479302
N2A	13745	41458;41459;41460	chr2:178614577;178614576;178614575	chr2:179479304;179479303;179479302
N2B	7248	21967;21968;21969	chr2:178614577;178614576;178614575	chr2:179479304;179479303;179479302
Novex-1	7373	22342;22343;22344	chr2:178614577;178614576;178614575	chr2:179479304;179479303;179479302
Novex-2	7440	22543;22544;22545	chr2:178614577;178614576;178614575	chr2:179479304;179479303;179479302
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-110
• Domain position: 52
• Structural Position: 135
• Q(SASA): 0.3989
• 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/I	None	None	0.927	N	0.481	0.313	0.493964856914	gnomAD-4.0.0	1.59406E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86256E-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
K/A	0.5113	ambiguous	0.4147	ambiguous	-0.312	Destabilizing	0.329	N	0.362	neutral	None	None	None	None	N
K/C	0.6227	likely_pathogenic	0.5478	ambiguous	-0.318	Destabilizing	0.995	D	0.447	neutral	None	None	None	None	N
K/D	0.7923	likely_pathogenic	0.7143	pathogenic	0.043	Stabilizing	0.495	N	0.405	neutral	None	None	None	None	N
K/E	0.3652	ambiguous	0.2756	benign	0.083	Stabilizing	0.27	N	0.265	neutral	N	0.469864189	None	None	N
K/F	0.7773	likely_pathogenic	0.7227	pathogenic	-0.368	Destabilizing	0.944	D	0.465	neutral	None	None	None	None	N
K/G	0.6739	likely_pathogenic	0.5871	pathogenic	-0.593	Destabilizing	0.495	N	0.472	neutral	None	None	None	None	N
K/H	0.2426	likely_benign	0.1979	benign	-1.066	Destabilizing	0.001	N	0.189	neutral	None	None	None	None	N
K/I	0.398	ambiguous	0.3279	benign	0.374	Stabilizing	0.927	D	0.481	neutral	N	0.465614651	None	None	N
K/L	0.4596	ambiguous	0.3927	ambiguous	0.374	Stabilizing	0.704	D	0.476	neutral	None	None	None	None	N
K/M	0.2763	likely_benign	0.2152	benign	0.392	Stabilizing	0.944	D	0.449	neutral	None	None	None	None	N
K/N	0.4785	ambiguous	0.4034	ambiguous	-0.005	Destabilizing	0.425	N	0.288	neutral	N	0.374612772	None	None	N
K/P	0.9786	likely_pathogenic	0.9734	pathogenic	0.175	Stabilizing	0.828	D	0.479	neutral	None	None	None	None	N
K/Q	0.1485	likely_benign	0.1183	benign	-0.225	Destabilizing	0.023	N	0.143	neutral	N	0.469389385	None	None	N
K/R	0.0973	likely_benign	0.0849	benign	-0.302	Destabilizing	0.27	N	0.305	neutral	N	0.452826008	None	None	N
K/S	0.5008	ambiguous	0.415	ambiguous	-0.629	Destabilizing	0.037	N	0.127	neutral	None	None	None	None	N
K/T	0.2151	likely_benign	0.1592	benign	-0.413	Destabilizing	0.27	N	0.401	neutral	N	0.429701722	None	None	N
K/V	0.3839	ambiguous	0.3069	benign	0.175	Stabilizing	0.828	D	0.475	neutral	None	None	None	None	N
K/W	0.8002	likely_pathogenic	0.7517	pathogenic	-0.261	Destabilizing	0.995	D	0.459	neutral	None	None	None	None	N
K/Y	0.5916	likely_pathogenic	0.5366	ambiguous	0.077	Stabilizing	0.704	D	0.509	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.