TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17383	52372;52373;52374	chr2:178608864;178608863;178608862	chr2:179473591;179473590;179473589
N2AB	15742	47449;47450;47451	chr2:178608864;178608863;178608862	chr2:179473591;179473590;179473589
N2A	14815	44668;44669;44670	chr2:178608864;178608863;178608862	chr2:179473591;179473590;179473589
N2B	8318	25177;25178;25179	chr2:178608864;178608863;178608862	chr2:179473591;179473590;179473589
Novex-1	8443	25552;25553;25554	chr2:178608864;178608863;178608862	chr2:179473591;179473590;179473589
Novex-2	8510	25753;25754;25755	chr2:178608864;178608863;178608862	chr2:179473591;179473590;179473589
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-14
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.417
• 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	0.999	N	0.585	0.444	0.277730125212	gnomAD-4.0.0	6.85179E-07	None	None	None	None	N	None	2.9967E-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
K/A	0.4651	ambiguous	0.4252	ambiguous	-0.329	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
K/C	0.7982	likely_pathogenic	0.7747	pathogenic	-0.449	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/D	0.7682	likely_pathogenic	0.7472	pathogenic	-0.471	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/E	0.4048	ambiguous	0.3711	ambiguous	-0.43	Destabilizing	0.999	D	0.585	neutral	N	0.468858058	None	None	N
K/F	0.9605	likely_pathogenic	0.9443	pathogenic	-0.404	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/G	0.5325	ambiguous	0.4845	ambiguous	-0.619	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
K/H	0.5217	ambiguous	0.475	ambiguous	-1.106	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
K/I	0.8024	likely_pathogenic	0.742	pathogenic	0.385	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/L	0.7555	likely_pathogenic	0.7054	pathogenic	0.385	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
K/M	0.5015	ambiguous	0.45	ambiguous	0.454	Stabilizing	1.0	D	0.631	neutral	N	0.48792933	None	None	N
K/N	0.4495	ambiguous	0.4374	ambiguous	-0.288	Destabilizing	1.0	D	0.751	deleterious	N	0.418162666	None	None	N
K/P	0.773	likely_pathogenic	0.7313	pathogenic	0.177	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
K/Q	0.2159	likely_benign	0.1909	benign	-0.548	Destabilizing	1.0	D	0.741	deleterious	N	0.485118377	None	None	N
K/R	0.1013	likely_benign	0.0918	benign	-0.415	Destabilizing	0.999	D	0.531	neutral	N	0.46330031	None	None	N
K/S	0.4746	ambiguous	0.4521	ambiguous	-0.825	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/T	0.4354	ambiguous	0.3916	ambiguous	-0.615	Destabilizing	1.0	D	0.711	prob.delet.	N	0.499084964	None	None	N
K/V	0.7217	likely_pathogenic	0.6555	pathogenic	0.177	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/W	0.9486	likely_pathogenic	0.9256	pathogenic	-0.313	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/Y	0.8566	likely_pathogenic	0.8276	pathogenic	0.041	Stabilizing	1.0	D	0.713	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.