TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22585	67978;67979;67980	chr2:178579277;178579276;178579275	chr2:179444004;179444003;179444002
N2AB	20944	63055;63056;63057	chr2:178579277;178579276;178579275	chr2:179444004;179444003;179444002
N2A	20017	60274;60275;60276	chr2:178579277;178579276;178579275	chr2:179444004;179444003;179444002
N2B	13520	40783;40784;40785	chr2:178579277;178579276;178579275	chr2:179444004;179444003;179444002
Novex-1	13645	41158;41159;41160	chr2:178579277;178579276;178579275	chr2:179444004;179444003;179444002
Novex-2	13712	41359;41360;41361	chr2:178579277;178579276;178579275	chr2:179444004;179444003;179444002
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: Ig-127
• Domain position: 26
• Structural Position: 49
• Q(SASA): 0.3862
• 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/N	rs2047135173	None	1.0	N	0.741	0.337	0.163833314356	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/R	None	None	0.999	N	0.543	0.224	0.197625483188	gnomAD-4.0.0	1.36881E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79929E-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
K/A	0.5632	ambiguous	0.5643	pathogenic	-0.849	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
K/C	0.6582	likely_pathogenic	0.6452	pathogenic	-1.252	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/D	0.8377	likely_pathogenic	0.8281	pathogenic	-1.001	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/E	0.2889	likely_benign	0.3044	benign	-0.857	Destabilizing	0.999	D	0.603	neutral	N	0.482605641	None	None	N
K/F	0.7001	likely_pathogenic	0.6848	pathogenic	-0.658	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/G	0.673	likely_pathogenic	0.649	pathogenic	-1.226	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/H	0.327	likely_benign	0.3054	benign	-1.622	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/I	0.3385	likely_benign	0.3406	ambiguous	0.145	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
K/L	0.3149	likely_benign	0.3194	benign	0.145	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/M	0.1945	likely_benign	0.1989	benign	0.016	Stabilizing	1.0	D	0.693	prob.neutral	N	0.505423786	None	None	N
K/N	0.5889	likely_pathogenic	0.563	ambiguous	-1.031	Destabilizing	1.0	D	0.741	deleterious	N	0.467288682	None	None	N
K/P	0.9891	likely_pathogenic	0.9879	pathogenic	-0.158	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/Q	0.1332	likely_benign	0.128	benign	-1.111	Destabilizing	1.0	D	0.733	prob.delet.	N	0.49930589	None	None	N
K/R	0.0815	likely_benign	0.0782	benign	-0.827	Destabilizing	0.999	D	0.543	neutral	N	0.490878408	None	None	N
K/S	0.5675	likely_pathogenic	0.5592	ambiguous	-1.644	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
K/T	0.2523	likely_benign	0.2621	benign	-1.284	Destabilizing	1.0	D	0.738	prob.delet.	N	0.445836765	None	None	N
K/V	0.3267	likely_benign	0.3361	benign	-0.158	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/W	0.7065	likely_pathogenic	0.6803	pathogenic	-0.586	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/Y	0.5908	likely_pathogenic	0.5683	pathogenic	-0.193	Destabilizing	1.0	D	0.727	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.