TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20064	60415;60416;60417	chr2:178591629;178591628;178591627	chr2:179456356;179456355;179456354
N2AB	18423	55492;55493;55494	chr2:178591629;178591628;178591627	chr2:179456356;179456355;179456354
N2A	17496	52711;52712;52713	chr2:178591629;178591628;178591627	chr2:179456356;179456355;179456354
N2B	10999	33220;33221;33222	chr2:178591629;178591628;178591627	chr2:179456356;179456355;179456354
Novex-1	11124	33595;33596;33597	chr2:178591629;178591628;178591627	chr2:179456356;179456355;179456354
Novex-2	11191	33796;33797;33798	chr2:178591629;178591628;178591627	chr2:179456356;179456355;179456354
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-33
• Domain position: 88
• Structural Position: 124
• Q(SASA): 0.2234
• 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
T/A	None	None	0.997	N	0.709	0.267	0.261217442401	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	5.66572E-05	0	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
T/A	0.3169	likely_benign	0.2682	benign	-0.878	Destabilizing	0.997	D	0.709	prob.delet.	N	0.476456034	None	None	N
T/C	0.8547	likely_pathogenic	0.8582	pathogenic	-0.525	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/D	0.9568	likely_pathogenic	0.946	pathogenic	-1.371	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
T/E	0.9633	likely_pathogenic	0.9545	pathogenic	-1.146	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
T/F	0.9674	likely_pathogenic	0.9573	pathogenic	-0.455	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
T/G	0.6834	likely_pathogenic	0.6432	pathogenic	-1.323	Destabilizing	0.999	D	0.737	deleterious	None	None	None	None	N
T/H	0.9604	likely_pathogenic	0.955	pathogenic	-1.454	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
T/I	0.8837	likely_pathogenic	0.8544	pathogenic	0.298	Stabilizing	0.999	D	0.815	deleterious	N	0.479245623	None	None	N
T/K	0.974	likely_pathogenic	0.9659	pathogenic	-0.4	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
T/L	0.6313	likely_pathogenic	0.5756	pathogenic	0.298	Stabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
T/M	0.511	ambiguous	0.4447	ambiguous	0.183	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/N	0.795	likely_pathogenic	0.7562	pathogenic	-1.173	Destabilizing	0.999	D	0.809	deleterious	N	0.472833134	None	None	N
T/P	0.8491	likely_pathogenic	0.8142	pathogenic	-0.062	Destabilizing	0.999	D	0.79	deleterious	N	0.457387484	None	None	N
T/Q	0.9468	likely_pathogenic	0.9343	pathogenic	-0.841	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
T/R	0.9648	likely_pathogenic	0.9562	pathogenic	-0.736	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
T/S	0.2749	likely_benign	0.2579	benign	-1.365	Destabilizing	0.997	D	0.733	deleterious	N	0.466028397	None	None	N
T/V	0.6345	likely_pathogenic	0.5942	pathogenic	-0.062	Destabilizing	0.998	D	0.818	deleterious	None	None	None	None	N
T/W	0.994	likely_pathogenic	0.9927	pathogenic	-0.725	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/Y	0.9782	likely_pathogenic	0.9733	pathogenic	-0.285	Destabilizing	1.0	D	0.791	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.