TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25312	76159;76160;76161	chr2:178570198;178570197;178570196	chr2:179434925;179434924;179434923
N2AB	23671	71236;71237;71238	chr2:178570198;178570197;178570196	chr2:179434925;179434924;179434923
N2A	22744	68455;68456;68457	chr2:178570198;178570197;178570196	chr2:179434925;179434924;179434923
N2B	16247	48964;48965;48966	chr2:178570198;178570197;178570196	chr2:179434925;179434924;179434923
Novex-1	16372	49339;49340;49341	chr2:178570198;178570197;178570196	chr2:179434925;179434924;179434923
Novex-2	16439	49540;49541;49542	chr2:178570198;178570197;178570196	chr2:179434925;179434924;179434923
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-72
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5892
• 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
E/K	rs770655678	0.368	0.999	N	0.628	0.39	0.287603790349	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
E/K	rs770655678	0.368	0.999	N	0.628	0.39	0.287603790349	gnomAD-4.0.0	2.05303E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69874E-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
E/A	0.157	likely_benign	0.176	benign	-0.343	Destabilizing	0.999	D	0.757	deleterious	N	0.477040324	None	None	N
E/C	0.7529	likely_pathogenic	0.8224	pathogenic	-0.115	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
E/D	0.1706	likely_benign	0.1952	benign	-0.443	Destabilizing	0.999	D	0.503	neutral	N	0.485358436	None	None	N
E/F	0.6905	likely_pathogenic	0.7479	pathogenic	-0.128	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/G	0.2938	likely_benign	0.3051	benign	-0.569	Destabilizing	1.0	D	0.777	deleterious	N	0.487511257	None	None	N
E/H	0.4054	ambiguous	0.4575	ambiguous	0.043	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/I	0.2167	likely_benign	0.2626	benign	0.226	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/K	0.1572	likely_benign	0.1614	benign	0.25	Stabilizing	0.999	D	0.628	neutral	N	0.501989197	None	None	N
E/L	0.3109	likely_benign	0.377	ambiguous	0.226	Stabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
E/M	0.3469	ambiguous	0.4077	ambiguous	0.253	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/N	0.2661	likely_benign	0.3068	benign	-0.125	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/P	0.9535	likely_pathogenic	0.9531	pathogenic	0.057	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/Q	0.1259	likely_benign	0.1397	benign	-0.07	Destabilizing	1.0	D	0.665	neutral	N	0.497911529	None	None	N
E/R	0.2626	likely_benign	0.2792	benign	0.482	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/S	0.1979	likely_benign	0.2251	benign	-0.281	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
E/T	0.1633	likely_benign	0.1904	benign	-0.097	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/V	0.1321	likely_benign	0.1574	benign	0.057	Stabilizing	1.0	D	0.837	deleterious	N	0.511880903	None	None	N
E/W	0.8909	likely_pathogenic	0.9132	pathogenic	0.036	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
E/Y	0.5883	likely_pathogenic	0.659	pathogenic	0.119	Stabilizing	1.0	D	0.827	deleterious	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.