TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32360	97303;97304;97305	chr2:178542776;178542775;178542774	chr2:179407503;179407502;179407501
N2AB	30719	92380;92381;92382	chr2:178542776;178542775;178542774	chr2:179407503;179407502;179407501
N2A	29792	89599;89600;89601	chr2:178542776;178542775;178542774	chr2:179407503;179407502;179407501
N2B	23295	70108;70109;70110	chr2:178542776;178542775;178542774	chr2:179407503;179407502;179407501
Novex-1	23420	70483;70484;70485	chr2:178542776;178542775;178542774	chr2:179407503;179407502;179407501
Novex-2	23487	70684;70685;70686	chr2:178542776;178542775;178542774	chr2:179407503;179407502;179407501
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-154
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.7783
• 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	0.996	N	0.625	0.44	0.376921832658	gnomAD-4.0.0	6.842E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99467E-07	0	0
K/Q	rs751750046	0.313	0.999	N	0.716	0.331	0.277730125212	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/Q	rs751750046	0.313	0.999	N	0.716	0.331	0.277730125212	gnomAD-4.0.0	2.0526E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	3.46861E-04	8.99467E-07	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	0.2307	likely_benign	0.2083	benign	0.016	Stabilizing	0.998	D	0.672	neutral	None	None	None	None	N
K/C	0.6794	likely_pathogenic	0.6435	pathogenic	-0.361	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/D	0.3335	likely_benign	0.3081	benign	0.017	Stabilizing	0.998	D	0.67	neutral	None	None	None	None	N
K/E	0.1605	likely_benign	0.139	benign	0.043	Stabilizing	0.996	D	0.625	neutral	N	0.45886843	None	None	N
K/F	0.7946	likely_pathogenic	0.7578	pathogenic	-0.093	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/G	0.2517	likely_benign	0.2309	benign	-0.203	Destabilizing	0.997	D	0.655	neutral	None	None	None	None	N
K/H	0.2897	likely_benign	0.2697	benign	-0.379	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/I	0.4549	ambiguous	0.4169	ambiguous	0.519	Stabilizing	1.0	D	0.717	prob.delet.	N	0.491655639	None	None	N
K/L	0.398	ambiguous	0.3556	ambiguous	0.519	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	N
K/M	0.2505	likely_benign	0.2259	benign	0.129	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/N	0.2677	likely_benign	0.2398	benign	0.009	Stabilizing	0.884	D	0.355	neutral	N	0.441533463	None	None	N
K/P	0.5602	ambiguous	0.5316	ambiguous	0.38	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/Q	0.132	likely_benign	0.1221	benign	-0.103	Destabilizing	0.999	D	0.716	prob.delet.	N	0.498080179	None	None	N
K/R	0.0797	likely_benign	0.0783	benign	-0.135	Destabilizing	0.998	D	0.591	neutral	N	0.484862952	None	None	N
K/S	0.2769	likely_benign	0.2424	benign	-0.448	Destabilizing	0.997	D	0.651	neutral	None	None	None	None	N
K/T	0.1397	likely_benign	0.1301	benign	-0.268	Destabilizing	0.999	D	0.669	neutral	N	0.470317574	None	None	N
K/V	0.3518	ambiguous	0.3214	benign	0.38	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/W	0.7494	likely_pathogenic	0.7261	pathogenic	-0.127	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/Y	0.6023	likely_pathogenic	0.5656	pathogenic	0.214	Stabilizing	1.0	D	0.709	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.