TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21664	65215;65216;65217	chr2:178584561;178584560;178584559	chr2:179449288;179449287;179449286
N2AB	20023	60292;60293;60294	chr2:178584561;178584560;178584559	chr2:179449288;179449287;179449286
N2A	19096	57511;57512;57513	chr2:178584561;178584560;178584559	chr2:179449288;179449287;179449286
N2B	12599	38020;38021;38022	chr2:178584561;178584560;178584559	chr2:179449288;179449287;179449286
Novex-1	12724	38395;38396;38397	chr2:178584561;178584560;178584559	chr2:179449288;179449287;179449286
Novex-2	12791	38596;38597;38598	chr2:178584561;178584560;178584559	chr2:179449288;179449287;179449286
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-45
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.4546
• 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/R	rs376637538	None	0.003	N	0.235	0.094	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs376637538	None	0.003	N	0.235	0.094	None	gnomAD-4.0.0	6.57436E-06	None	None	None	None	N	None	2.41324E-05	0	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
K/A	0.3659	ambiguous	0.3961	ambiguous	-0.36	Destabilizing	0.345	N	0.422	neutral	None	None	None	None	N
K/C	0.5984	likely_pathogenic	0.5974	pathogenic	-0.316	Destabilizing	0.991	D	0.571	neutral	None	None	None	None	N
K/D	0.791	likely_pathogenic	0.8263	pathogenic	-0.529	Destabilizing	0.39	N	0.512	neutral	None	None	None	None	N
K/E	0.235	likely_benign	0.2683	benign	-0.441	Destabilizing	0.003	N	0.172	neutral	N	0.396381884	None	None	N
K/F	0.8372	likely_pathogenic	0.8555	pathogenic	-0.08	Destabilizing	0.818	D	0.578	neutral	None	None	None	None	N
K/G	0.4016	ambiguous	0.4282	ambiguous	-0.725	Destabilizing	0.561	D	0.559	neutral	None	None	None	None	N
K/H	0.4243	ambiguous	0.4429	ambiguous	-1.228	Destabilizing	0.901	D	0.579	neutral	None	None	None	None	N
K/I	0.4437	ambiguous	0.4695	ambiguous	0.583	Stabilizing	0.017	N	0.451	neutral	None	None	None	None	N
K/L	0.3668	ambiguous	0.3907	ambiguous	0.583	Stabilizing	0.002	N	0.328	neutral	None	None	None	None	N
K/M	0.3124	likely_benign	0.3322	benign	0.579	Stabilizing	0.772	D	0.58	neutral	N	0.443330469	None	None	N
K/N	0.6078	likely_pathogenic	0.6443	pathogenic	-0.485	Destabilizing	0.491	N	0.489	neutral	N	0.461396155	None	None	N
K/P	0.8328	likely_pathogenic	0.8516	pathogenic	0.299	Stabilizing	0.901	D	0.615	neutral	None	None	None	None	N
K/Q	0.1551	likely_benign	0.1628	benign	-0.583	Destabilizing	0.036	N	0.275	neutral	N	0.37768148	None	None	N
K/R	0.0758	likely_benign	0.0762	benign	-0.746	Destabilizing	0.003	N	0.235	neutral	N	0.369619357	None	None	N
K/S	0.4979	ambiguous	0.5323	ambiguous	-0.976	Destabilizing	0.561	D	0.381	neutral	None	None	None	None	N
K/T	0.2321	likely_benign	0.2461	benign	-0.699	Destabilizing	0.491	N	0.503	neutral	N	0.403115856	None	None	N
K/V	0.3332	likely_benign	0.3562	ambiguous	0.299	Stabilizing	0.209	N	0.474	neutral	None	None	None	None	N
K/W	0.7835	likely_pathogenic	0.8054	pathogenic	-0.037	Destabilizing	0.991	D	0.601	neutral	None	None	None	None	N
K/Y	0.7298	likely_pathogenic	0.7546	pathogenic	0.265	Stabilizing	0.965	D	0.569	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.