TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15385	46378;46379;46380	chr2:178620368;178620367;178620366	chr2:179485095;179485094;179485093
N2AB	13744	41455;41456;41457	chr2:178620368;178620367;178620366	chr2:179485095;179485094;179485093
N2A	12817	38674;38675;38676	chr2:178620368;178620367;178620366	chr2:179485095;179485094;179485093
N2B	6320	19183;19184;19185	chr2:178620368;178620367;178620366	chr2:179485095;179485094;179485093
Novex-1	6445	19558;19559;19560	chr2:178620368;178620367;178620366	chr2:179485095;179485094;179485093
Novex-2	6512	19759;19760;19761	chr2:178620368;178620367;178620366	chr2:179485095;179485094;179485093
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-105
• Domain position: 84
• Structural Position: 175
• Q(SASA): 0.4519
• 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
L/F	rs2058085346	None	0.982	N	0.407	0.214	0.553063759574	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs2058085346	None	0.982	N	0.407	0.214	0.553063759574	gnomAD-4.0.0	6.58285E-06	None	None	None	None	N	None	2.41511E-05	0	None	0	0	None	0	0	0	0	0
L/R	None	None	0.997	N	0.542	0.433	0.66790570697	gnomAD-4.0.0	1.59966E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87237E-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
L/A	0.4334	ambiguous	0.4186	ambiguous	-1.522	Destabilizing	0.953	D	0.354	neutral	None	None	None	None	N
L/C	0.6543	likely_pathogenic	0.7007	pathogenic	-0.886	Destabilizing	0.999	D	0.473	neutral	None	None	None	None	N
L/D	0.7964	likely_pathogenic	0.7898	pathogenic	-0.979	Destabilizing	0.998	D	0.61	neutral	None	None	None	None	N
L/E	0.5033	ambiguous	0.4942	ambiguous	-0.959	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	N
L/F	0.2497	likely_benign	0.2502	benign	-0.918	Destabilizing	0.982	D	0.407	neutral	N	0.447413739	None	None	N
L/G	0.7204	likely_pathogenic	0.7037	pathogenic	-1.853	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	N
L/H	0.3266	likely_benign	0.2967	benign	-0.959	Destabilizing	0.999	D	0.619	neutral	N	0.451562543	None	None	N
L/I	0.1092	likely_benign	0.105	benign	-0.681	Destabilizing	0.02	N	0.135	neutral	N	0.355263859	None	None	N
L/K	0.3482	ambiguous	0.2801	benign	-1.117	Destabilizing	0.993	D	0.528	neutral	None	None	None	None	N
L/M	0.1569	likely_benign	0.1622	benign	-0.563	Destabilizing	0.986	D	0.439	neutral	None	None	None	None	N
L/N	0.4459	ambiguous	0.4339	ambiguous	-0.975	Destabilizing	0.998	D	0.619	neutral	None	None	None	None	N
L/P	0.9501	likely_pathogenic	0.945	pathogenic	-0.93	Destabilizing	0.997	D	0.616	neutral	N	0.453420042	None	None	N
L/Q	0.2408	likely_benign	0.24	benign	-1.119	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	N
L/R	0.2776	likely_benign	0.2463	benign	-0.51	Destabilizing	0.997	D	0.542	neutral	N	0.449432501	None	None	N
L/S	0.4804	ambiguous	0.4692	ambiguous	-1.576	Destabilizing	0.993	D	0.504	neutral	None	None	None	None	N
L/T	0.3559	ambiguous	0.3257	benign	-1.44	Destabilizing	0.986	D	0.423	neutral	None	None	None	None	N
L/V	0.1524	likely_benign	0.1508	benign	-0.93	Destabilizing	0.76	D	0.257	neutral	N	0.43588444	None	None	N
L/W	0.4266	ambiguous	0.4174	ambiguous	-1.006	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	N
L/Y	0.4846	ambiguous	0.4908	ambiguous	-0.79	Destabilizing	0.998	D	0.438	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.