TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19638	59137;59138;59139	chr2:178593296;178593295;178593294	chr2:179458023;179458022;179458021
N2AB	17997	54214;54215;54216	chr2:178593296;178593295;178593294	chr2:179458023;179458022;179458021
N2A	17070	51433;51434;51435	chr2:178593296;178593295;178593294	chr2:179458023;179458022;179458021
N2B	10573	31942;31943;31944	chr2:178593296;178593295;178593294	chr2:179458023;179458022;179458021
Novex-1	10698	32317;32318;32319	chr2:178593296;178593295;178593294	chr2:179458023;179458022;179458021
Novex-2	10765	32518;32519;32520	chr2:178593296;178593295;178593294	chr2:179458023;179458022;179458021
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: Fn3-30
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.4733
• 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/I	rs1257692385	0.765	0.966	N	0.636	0.476	0.675970969783	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/I	rs1257692385	0.765	0.966	N	0.636	0.476	0.675970969783	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-05	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	0.3411	ambiguous	0.3983	ambiguous	-0.763	Destabilizing	0.688	D	0.505	neutral	None	None	None	None	N
K/C	0.629	likely_pathogenic	0.6951	pathogenic	-0.705	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	N
K/D	0.6194	likely_pathogenic	0.6757	pathogenic	0.067	Stabilizing	0.728	D	0.519	neutral	None	None	None	None	N
K/E	0.2106	likely_benign	0.2449	benign	0.241	Stabilizing	0.022	N	0.298	neutral	N	0.405886802	None	None	N
K/F	0.8308	likely_pathogenic	0.865	pathogenic	-0.317	Destabilizing	0.991	D	0.637	neutral	None	None	None	None	N
K/G	0.5472	ambiguous	0.5979	pathogenic	-1.146	Destabilizing	0.842	D	0.558	neutral	None	None	None	None	N
K/H	0.2884	likely_benign	0.3287	benign	-1.089	Destabilizing	0.974	D	0.595	neutral	None	None	None	None	N
K/I	0.3979	ambiguous	0.4506	ambiguous	0.257	Stabilizing	0.966	D	0.636	neutral	N	0.494892653	None	None	N
K/L	0.4606	ambiguous	0.5052	ambiguous	0.257	Stabilizing	0.842	D	0.563	neutral	None	None	None	None	N
K/M	0.2759	likely_benign	0.3093	benign	-0.1	Destabilizing	0.974	D	0.593	neutral	None	None	None	None	N
K/N	0.4504	ambiguous	0.519	ambiguous	-0.536	Destabilizing	0.801	D	0.467	neutral	N	0.477325613	None	None	N
K/P	0.9433	likely_pathogenic	0.9421	pathogenic	-0.055	Destabilizing	0.974	D	0.595	neutral	None	None	None	None	N
K/Q	0.1174	likely_benign	0.1387	benign	-0.442	Destabilizing	0.051	N	0.298	neutral	N	0.423376484	None	None	N
K/R	0.0773	likely_benign	0.0779	benign	-0.258	Destabilizing	0.669	D	0.517	neutral	N	0.421432257	None	None	N
K/S	0.3601	ambiguous	0.4254	ambiguous	-1.242	Destabilizing	0.842	D	0.503	neutral	None	None	None	None	N
K/T	0.1451	likely_benign	0.1693	benign	-0.839	Destabilizing	0.801	D	0.515	neutral	N	0.426760719	None	None	N
K/V	0.3072	likely_benign	0.3397	benign	-0.055	Destabilizing	0.915	D	0.592	neutral	None	None	None	None	N
K/W	0.8438	likely_pathogenic	0.8661	pathogenic	-0.208	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
K/Y	0.6241	likely_pathogenic	0.6785	pathogenic	0.075	Stabilizing	0.991	D	0.633	neutral	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.