TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14461	43606;43607;43608	chr2:178632625;178632624;178632623	chr2:179497352;179497351;179497350
N2AB	12820	38683;38684;38685	chr2:178632625;178632624;178632623	chr2:179497352;179497351;179497350
N2A	11893	35902;35903;35904	chr2:178632625;178632624;178632623	chr2:179497352;179497351;179497350
N2B	5396	16411;16412;16413	chr2:178632625;178632624;178632623	chr2:179497352;179497351;179497350
Novex-1	5521	16786;16787;16788	chr2:178632625;178632624;178632623	chr2:179497352;179497351;179497350
Novex-2	5588	16987;16988;16989	chr2:178632625;178632624;178632623	chr2:179497352;179497351;179497350
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: Ig-95
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.3802
• 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/E	None	None	0.124	N	0.458	0.092	0.210429274316	gnomAD-4.0.0	1.59181E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85953E-06	0	0
K/R	rs887333870	None	None	N	0.11	0.167	0.0716867268079	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/R	rs887333870	None	None	N	0.11	0.167	0.0716867268079	gnomAD-4.0.0	2.47924E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39093E-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	0.3931	ambiguous	0.4141	ambiguous	-0.303	Destabilizing	0.272	N	0.549	neutral	None	None	None	None	N
K/C	0.6295	likely_pathogenic	0.5963	pathogenic	-0.361	Destabilizing	0.968	D	0.73	prob.delet.	None	None	None	None	N
K/D	0.7395	likely_pathogenic	0.7616	pathogenic	-0.727	Destabilizing	0.567	D	0.643	neutral	None	None	None	None	N
K/E	0.2166	likely_benign	0.234	benign	-0.655	Destabilizing	0.124	N	0.458	neutral	N	0.506656739	None	None	N
K/F	0.7356	likely_pathogenic	0.7416	pathogenic	-0.225	Destabilizing	0.726	D	0.731	prob.delet.	None	None	None	None	N
K/G	0.4429	ambiguous	0.4756	ambiguous	-0.642	Destabilizing	0.272	N	0.667	neutral	None	None	None	None	N
K/H	0.3154	likely_benign	0.3154	benign	-1.149	Destabilizing	0.726	D	0.671	neutral	None	None	None	None	N
K/I	0.2712	likely_benign	0.2802	benign	0.561	Stabilizing	0.726	D	0.733	prob.delet.	None	None	None	None	N
K/L	0.3545	ambiguous	0.3612	ambiguous	0.561	Stabilizing	0.272	N	0.667	neutral	None	None	None	None	N
K/M	0.2351	likely_benign	0.2333	benign	0.653	Stabilizing	0.958	D	0.654	neutral	N	0.504746739	None	None	N
K/N	0.4936	ambiguous	0.5285	ambiguous	-0.477	Destabilizing	0.22	N	0.497	neutral	N	0.505731355	None	None	N
K/P	0.9201	likely_pathogenic	0.9297	pathogenic	0.303	Stabilizing	0.726	D	0.683	prob.neutral	None	None	None	None	N
K/Q	0.138	likely_benign	0.1399	benign	-0.654	Destabilizing	0.22	N	0.525	neutral	N	0.508314478	None	None	N
K/R	0.0568	likely_benign	0.0576	benign	-0.564	Destabilizing	None	N	0.11	neutral	N	0.445470887	None	None	N
K/S	0.4553	ambiguous	0.4722	ambiguous	-0.945	Destabilizing	0.272	N	0.444	neutral	None	None	None	None	N
K/T	0.1885	likely_benign	0.1927	benign	-0.693	Destabilizing	0.22	N	0.625	neutral	N	0.48540887	None	None	N
K/V	0.2739	likely_benign	0.2788	benign	0.303	Stabilizing	0.567	D	0.674	neutral	None	None	None	None	N
K/W	0.6336	likely_pathogenic	0.6193	pathogenic	-0.197	Destabilizing	0.968	D	0.717	prob.delet.	None	None	None	None	N
K/Y	0.5968	likely_pathogenic	0.5985	pathogenic	0.164	Stabilizing	0.726	D	0.727	prob.delet.	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.