TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19574	58945;58946;58947	chr2:178593580;178593579;178593578	chr2:179458307;179458306;179458305
N2AB	17933	54022;54023;54024	chr2:178593580;178593579;178593578	chr2:179458307;179458306;179458305
N2A	17006	51241;51242;51243	chr2:178593580;178593579;178593578	chr2:179458307;179458306;179458305
N2B	10509	31750;31751;31752	chr2:178593580;178593579;178593578	chr2:179458307;179458306;179458305
Novex-1	10634	32125;32126;32127	chr2:178593580;178593579;178593578	chr2:179458307;179458306;179458305
Novex-2	10701	32326;32327;32328	chr2:178593580;178593579;178593578	chr2:179458307;179458306;179458305
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-29
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.4902
• 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	rs1032128606	None	0.104	N	0.431	0.246	0.27132560031	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs1032128606	None	0.104	N	0.431	0.246	0.27132560031	gnomAD-4.0.0	6.57376E-06	None	None	None	None	N	None	2.41266E-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	0.3896	ambiguous	0.3864	ambiguous	-0.2	Destabilizing	0.236	N	0.479	neutral	None	None	None	None	N
K/C	0.6444	likely_pathogenic	0.661	pathogenic	-0.317	Destabilizing	0.962	D	0.76	deleterious	None	None	None	None	N
K/D	0.8064	likely_pathogenic	0.807	pathogenic	0.017	Stabilizing	0.519	D	0.552	neutral	None	None	None	None	N
K/E	0.2018	likely_benign	0.2001	benign	0.07	Stabilizing	0.104	N	0.431	neutral	N	0.493019709	None	None	N
K/F	0.7941	likely_pathogenic	0.7914	pathogenic	-0.074	Destabilizing	0.892	D	0.727	deleterious	None	None	None	None	N
K/G	0.5907	likely_pathogenic	0.5749	pathogenic	-0.498	Destabilizing	0.519	D	0.451	neutral	None	None	None	None	N
K/H	0.4167	ambiguous	0.426	ambiguous	-0.845	Destabilizing	0.892	D	0.501	neutral	None	None	None	None	N
K/I	0.3469	ambiguous	0.3647	ambiguous	0.534	Stabilizing	0.623	D	0.78	deleterious	N	0.505785274	None	None	N
K/L	0.4638	ambiguous	0.4536	ambiguous	0.534	Stabilizing	0.519	D	0.451	neutral	None	None	None	None	N
K/M	0.2528	likely_benign	0.2562	benign	0.337	Stabilizing	0.962	D	0.493	neutral	None	None	None	None	N
K/N	0.6467	likely_pathogenic	0.6684	pathogenic	-0.041	Destabilizing	0.449	N	0.575	neutral	N	0.515874132	None	None	N
K/P	0.9744	likely_pathogenic	0.9686	pathogenic	0.32	Stabilizing	0.687	D	0.538	neutral	None	None	None	None	N
K/Q	0.1395	likely_benign	0.1453	benign	-0.195	Destabilizing	0.29	N	0.601	neutral	N	0.512508127	None	None	N
K/R	0.0798	likely_benign	0.0797	benign	-0.362	Destabilizing	0.001	N	0.203	neutral	N	0.483705372	None	None	N
K/S	0.5223	ambiguous	0.5307	ambiguous	-0.607	Destabilizing	0.236	N	0.602	neutral	None	None	None	None	N
K/T	0.1955	likely_benign	0.2052	benign	-0.379	Destabilizing	0.449	N	0.529	neutral	N	0.490172554	None	None	N
K/V	0.2743	likely_benign	0.2829	benign	0.32	Stabilizing	0.519	D	0.705	prob.delet.	None	None	None	None	N
K/W	0.8112	likely_pathogenic	0.7969	pathogenic	0.013	Stabilizing	0.962	D	0.757	deleterious	None	None	None	None	N
K/Y	0.7106	likely_pathogenic	0.7158	pathogenic	0.31	Stabilizing	0.687	D	0.694	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.