TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19575	58948;58949;58950	chr2:178593577;178593576;178593575	chr2:179458304;179458303;179458302
N2AB	17934	54025;54026;54027	chr2:178593577;178593576;178593575	chr2:179458304;179458303;179458302
N2A	17007	51244;51245;51246	chr2:178593577;178593576;178593575	chr2:179458304;179458303;179458302
N2B	10510	31753;31754;31755	chr2:178593577;178593576;178593575	chr2:179458304;179458303;179458302
Novex-1	10635	32128;32129;32130	chr2:178593577;178593576;178593575	chr2:179458304;179458303;179458302
Novex-2	10702	32329;32330;32331	chr2:178593577;178593576;178593575	chr2:179458304;179458303;179458302
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-29
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.8436
• 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
D/Y	rs748522705	0.109	0.995	N	0.771	0.464	0.426670027402	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	2.93E-05	None	0	0	None	0	None	0	0	0
D/Y	rs748522705	0.109	0.995	N	0.771	0.464	0.426670027402	gnomAD-4.0.0	1.5961E-06	None	None	None	None	N	None	0	2.30213E-05	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
D/A	0.7198	likely_pathogenic	0.6533	pathogenic	-0.043	Destabilizing	0.804	D	0.605	neutral	N	0.519874029	None	None	N
D/C	0.9145	likely_pathogenic	0.8892	pathogenic	-0.03	Destabilizing	0.996	D	0.829	deleterious	None	None	None	None	N
D/E	0.6728	likely_pathogenic	0.5993	pathogenic	-0.215	Destabilizing	0.007	N	0.365	neutral	D	0.530917742	None	None	N
D/F	0.9235	likely_pathogenic	0.9013	pathogenic	-0.073	Destabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
D/G	0.6183	likely_pathogenic	0.5567	ambiguous	-0.199	Destabilizing	0.7	D	0.722	deleterious	N	0.485271028	None	None	N
D/H	0.7781	likely_pathogenic	0.7302	pathogenic	0.282	Stabilizing	0.984	D	0.825	deleterious	N	0.510833258	None	None	N
D/I	0.8961	likely_pathogenic	0.8682	pathogenic	0.304	Stabilizing	0.956	D	0.776	deleterious	None	None	None	None	N
D/K	0.9437	likely_pathogenic	0.9322	pathogenic	0.38	Stabilizing	0.844	D	0.752	deleterious	None	None	None	None	N
D/L	0.8556	likely_pathogenic	0.8242	pathogenic	0.304	Stabilizing	0.916	D	0.709	prob.delet.	None	None	None	None	N
D/M	0.9455	likely_pathogenic	0.9268	pathogenic	0.205	Stabilizing	0.996	D	0.823	deleterious	None	None	None	None	N
D/N	0.2502	likely_benign	0.2188	benign	0.194	Stabilizing	0.891	D	0.768	deleterious	N	0.495325088	None	None	N
D/P	0.9344	likely_pathogenic	0.9276	pathogenic	0.209	Stabilizing	0.956	D	0.775	deleterious	None	None	None	None	N
D/Q	0.9031	likely_pathogenic	0.875	pathogenic	0.203	Stabilizing	0.844	D	0.797	deleterious	None	None	None	None	N
D/R	0.9525	likely_pathogenic	0.9423	pathogenic	0.577	Stabilizing	0.916	D	0.723	deleterious	None	None	None	None	N
D/S	0.4468	ambiguous	0.387	ambiguous	0.073	Stabilizing	0.607	D	0.689	prob.delet.	None	None	None	None	N
D/T	0.7106	likely_pathogenic	0.6765	pathogenic	0.191	Stabilizing	0.916	D	0.77	deleterious	None	None	None	None	N
D/V	0.7521	likely_pathogenic	0.6977	pathogenic	0.209	Stabilizing	0.891	D	0.719	prob.delet.	N	0.493918309	None	None	N
D/W	0.9761	likely_pathogenic	0.9737	pathogenic	-0.005	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
D/Y	0.5565	ambiguous	0.5162	ambiguous	0.155	Stabilizing	0.995	D	0.771	deleterious	N	0.489996626	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.