TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6209	18850;18851;18852	chr2:178729531;178729530;178729529	chr2:179594258;179594257;179594256
N2AB	5892	17899;17900;17901	chr2:178729531;178729530;178729529	chr2:179594258;179594257;179594256
N2A	4965	15118;15119;15120	chr2:178729531;178729530;178729529	chr2:179594258;179594257;179594256
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-46
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.7231
• 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	rs751253663	0.711	0.998	N	0.583	0.404	0.527356302626	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs751253663	0.711	0.998	N	0.583	0.404	0.527356302626	gnomAD-4.0.0	1.59212E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-05	0
E/Q	rs751253663	0.25	0.999	D	0.675	0.355	0.419713421852	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/Q	rs751253663	0.25	0.999	D	0.675	0.355	0.419713421852	gnomAD-4.0.0	1.59212E-06	None	None	None	None	N	None	0	2.28749E-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
E/A	0.189	likely_benign	0.1772	benign	-0.374	Destabilizing	0.998	D	0.636	neutral	N	0.502352635	None	None	N
E/C	0.9028	likely_pathogenic	0.8832	pathogenic	-0.086	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/D	0.1342	likely_benign	0.1258	benign	-0.409	Destabilizing	0.434	N	0.246	neutral	N	0.481940077	None	None	N
E/F	0.8176	likely_pathogenic	0.7864	pathogenic	-0.19	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/G	0.2839	likely_benign	0.2727	benign	-0.587	Destabilizing	0.999	D	0.649	neutral	N	0.493622956	None	None	N
E/H	0.5747	likely_pathogenic	0.5062	ambiguous	0.039	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/I	0.48	ambiguous	0.4414	ambiguous	0.157	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/K	0.2981	likely_benign	0.2587	benign	0.323	Stabilizing	0.998	D	0.583	neutral	N	0.520957039	None	None	N
E/L	0.5238	ambiguous	0.4725	ambiguous	0.157	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/M	0.5637	ambiguous	0.5065	ambiguous	0.212	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
E/N	0.3175	likely_benign	0.2839	benign	-0.062	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
E/P	0.7651	likely_pathogenic	0.7414	pathogenic	0.001	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
E/Q	0.2127	likely_benign	0.1863	benign	-0.02	Destabilizing	0.999	D	0.675	neutral	D	0.528192442	None	None	N
E/R	0.4464	ambiguous	0.3857	ambiguous	0.552	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/S	0.2425	likely_benign	0.2234	benign	-0.217	Destabilizing	0.997	D	0.618	neutral	None	None	None	None	N
E/T	0.2549	likely_benign	0.2263	benign	-0.042	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/V	0.2628	likely_benign	0.2377	benign	0.001	Stabilizing	1.0	D	0.69	prob.neutral	N	0.493058361	None	None	N
E/W	0.9229	likely_pathogenic	0.9027	pathogenic	-0.02	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
E/Y	0.7089	likely_pathogenic	0.6584	pathogenic	0.063	Stabilizing	1.0	D	0.694	prob.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.