TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25314	76165;76166;76167	chr2:178570192;178570191;178570190	chr2:179434919;179434918;179434917
N2AB	23673	71242;71243;71244	chr2:178570192;178570191;178570190	chr2:179434919;179434918;179434917
N2A	22746	68461;68462;68463	chr2:178570192;178570191;178570190	chr2:179434919;179434918;179434917
N2B	16249	48970;48971;48972	chr2:178570192;178570191;178570190	chr2:179434919;179434918;179434917
Novex-1	16374	49345;49346;49347	chr2:178570192;178570191;178570190	chr2:179434919;179434918;179434917
Novex-2	16441	49546;49547;49548	chr2:178570192;178570191;178570190	chr2:179434919;179434918;179434917
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-72
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.317
• 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
T/I	rs1707646875	None	0.984	D	0.599	0.407	0.508517017164	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1707646875	None	0.984	D	0.599	0.407	0.508517017164	gnomAD-4.0.0	6.57661E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4708E-05	0	0
T/S	None	None	0.046	N	0.167	0.077	0.203808441222	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

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
T/A	0.1291	likely_benign	0.1236	benign	-0.532	Destabilizing	0.64	D	0.412	neutral	N	0.470611997	None	None	N
T/C	0.5164	ambiguous	0.5565	ambiguous	-0.394	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
T/D	0.6743	likely_pathogenic	0.6397	pathogenic	0.096	Stabilizing	0.919	D	0.598	neutral	None	None	None	None	N
T/E	0.5963	likely_pathogenic	0.5519	ambiguous	0.076	Stabilizing	0.919	D	0.601	neutral	None	None	None	None	N
T/F	0.3625	ambiguous	0.3888	ambiguous	-0.702	Destabilizing	0.996	D	0.72	prob.delet.	None	None	None	None	N
T/G	0.3128	likely_benign	0.322	benign	-0.757	Destabilizing	0.851	D	0.607	neutral	None	None	None	None	N
T/H	0.4519	ambiguous	0.4611	ambiguous	-0.992	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
T/I	0.2987	likely_benign	0.2802	benign	-0.038	Destabilizing	0.984	D	0.599	neutral	D	0.5246582	None	None	N
T/K	0.4567	ambiguous	0.4323	ambiguous	-0.6	Destabilizing	0.896	D	0.597	neutral	N	0.518038872	None	None	N
T/L	0.1544	likely_benign	0.1531	benign	-0.038	Destabilizing	0.919	D	0.573	neutral	None	None	None	None	N
T/M	0.1216	likely_benign	0.1187	benign	0.063	Stabilizing	0.999	D	0.658	neutral	None	None	None	None	N
T/N	0.2028	likely_benign	0.1984	benign	-0.497	Destabilizing	0.919	D	0.541	neutral	None	None	None	None	N
T/P	0.5984	likely_pathogenic	0.5346	ambiguous	-0.17	Destabilizing	0.984	D	0.596	neutral	N	0.491464957	None	None	N
T/Q	0.4101	ambiguous	0.3977	ambiguous	-0.631	Destabilizing	0.988	D	0.658	neutral	None	None	None	None	N
T/R	0.4274	ambiguous	0.4097	ambiguous	-0.365	Destabilizing	0.968	D	0.641	neutral	N	0.480802987	None	None	N
T/S	0.1266	likely_benign	0.1299	benign	-0.751	Destabilizing	0.046	N	0.167	neutral	N	0.425280639	None	None	N
T/V	0.2108	likely_benign	0.2074	benign	-0.17	Destabilizing	0.919	D	0.513	neutral	None	None	None	None	N
T/W	0.7858	likely_pathogenic	0.813	pathogenic	-0.69	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
T/Y	0.4545	ambiguous	0.4852	ambiguous	-0.434	Destabilizing	0.996	D	0.723	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.