TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2601	8026;8027;8028	chr2:178773163;178773162;178773161	chr2:179637890;179637889;179637888
N2AB	2601	8026;8027;8028	chr2:178773163;178773162;178773161	chr2:179637890;179637889;179637888
N2A	2601	8026;8027;8028	chr2:178773163;178773162;178773161	chr2:179637890;179637889;179637888
N2B	2555	7888;7889;7890	chr2:178773163;178773162;178773161	chr2:179637890;179637889;179637888
Novex-1	2555	7888;7889;7890	chr2:178773163;178773162;178773161	chr2:179637890;179637889;179637888
Novex-2	2555	7888;7889;7890	chr2:178773163;178773162;178773161	chr2:179637890;179637889;179637888
Novex-3	2601	8026;8027;8028	chr2:178773163;178773162;178773161	chr2:179637890;179637889;179637888

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-15
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.4242
• 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/N	rs988264686	-0.622	0.007	N	0.321	0.072	0.184867976434	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/N	rs988264686	-0.622	0.007	N	0.321	0.072	0.184867976434	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	2.28802E-05	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	0.1247	likely_benign	0.1533	benign	-0.727	Destabilizing	0.004	N	0.247	neutral	None	None	None	None	N
K/C	0.4701	ambiguous	0.5411	ambiguous	-0.708	Destabilizing	0.788	D	0.488	neutral	None	None	None	None	N
K/D	0.1581	likely_benign	0.1883	benign	-0.054	Destabilizing	None	N	0.176	neutral	None	None	None	None	N
K/E	0.0545	likely_benign	0.0688	benign	0.051	Stabilizing	None	N	0.119	neutral	N	0.294296712	None	None	N
K/F	0.4689	ambiguous	0.5121	ambiguous	-0.5	Destabilizing	0.138	N	0.581	neutral	None	None	None	None	N
K/G	0.2244	likely_benign	0.2666	benign	-1.082	Destabilizing	0.018	N	0.295	neutral	None	None	None	None	N
K/H	0.203	likely_benign	0.2361	benign	-1.419	Destabilizing	0.138	N	0.467	neutral	None	None	None	None	N
K/I	0.1075	likely_benign	0.1261	benign	0.19	Stabilizing	0.017	N	0.503	neutral	N	0.473445403	None	None	N
K/L	0.1287	likely_benign	0.1544	benign	0.19	Stabilizing	None	N	0.255	neutral	None	None	None	None	N
K/M	0.1042	likely_benign	0.1242	benign	0.172	Stabilizing	0.138	N	0.463	neutral	None	None	None	None	N
K/N	0.1227	likely_benign	0.143	benign	-0.423	Destabilizing	0.007	N	0.321	neutral	N	0.485417275	None	None	N
K/P	0.3428	ambiguous	0.3952	ambiguous	-0.086	Destabilizing	0.085	N	0.425	neutral	None	None	None	None	N
K/Q	0.0841	likely_benign	0.1041	benign	-0.548	Destabilizing	None	N	0.111	neutral	N	0.38680643	None	None	N
K/R	0.0954	likely_benign	0.1123	benign	-0.557	Destabilizing	0.007	N	0.323	neutral	N	0.440572741	None	None	N
K/S	0.152	likely_benign	0.1792	benign	-1.172	Destabilizing	0.004	N	0.222	neutral	None	None	None	None	N
K/T	0.0708	likely_benign	0.0834	benign	-0.855	Destabilizing	0.014	N	0.334	neutral	N	0.380129835	None	None	N
K/V	0.1026	likely_benign	0.1255	benign	-0.086	Destabilizing	0.009	N	0.321	neutral	None	None	None	None	N
K/W	0.6093	likely_pathogenic	0.6511	pathogenic	-0.316	Destabilizing	0.788	D	0.493	neutral	None	None	None	None	N
K/Y	0.3318	likely_benign	0.3686	ambiguous	-0.023	Destabilizing	0.085	N	0.57	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.