TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7990	24193;24194;24195	chr2:178719422;178719421;178719420	chr2:179584149;179584148;179584147
N2AB	7673	23242;23243;23244	chr2:178719422;178719421;178719420	chr2:179584149;179584148;179584147
N2A	6746	20461;20462;20463	chr2:178719422;178719421;178719420	chr2:179584149;179584148;179584147
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-65
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6829
• Predicted PPI site: I

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	None	None	0.062	N	0.489	0.215	0.350524144436	gnomAD-4.0.0	6.84526E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99936E-07	0	0
K/Q	rs1164743322	0.018	0.317	N	0.511	0.187	0.250579442822	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/Q	rs1164743322	0.018	0.317	N	0.511	0.187	0.250579442822	gnomAD-4.0.0	2.05358E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	3.47915E-05	0
K/R	None	None	None	N	0.195	0.137	0.290222751274	gnomAD-4.0.0	2.73809E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79987E-06	0	3.31389E-05

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	0.3924	ambiguous	0.5315	ambiguous	-0.452	Destabilizing	0.067	N	0.47	neutral	None	None	None	None	I
K/C	0.694	likely_pathogenic	0.8257	pathogenic	-0.475	Destabilizing	0.935	D	0.565	neutral	None	None	None	None	I
K/D	0.6005	likely_pathogenic	0.7402	pathogenic	0.226	Stabilizing	0.149	N	0.487	neutral	None	None	None	None	I
K/E	0.214	likely_benign	0.2909	benign	0.331	Stabilizing	0.062	N	0.489	neutral	N	0.51826345	None	None	I
K/F	0.7406	likely_pathogenic	0.8721	pathogenic	-0.138	Destabilizing	0.555	D	0.543	neutral	None	None	None	None	I
K/G	0.4162	ambiguous	0.5643	pathogenic	-0.794	Destabilizing	0.149	N	0.507	neutral	None	None	None	None	I
K/H	0.283	likely_benign	0.3993	ambiguous	-0.964	Destabilizing	0.555	D	0.508	neutral	None	None	None	None	I
K/I	0.4126	ambiguous	0.5735	pathogenic	0.421	Stabilizing	0.555	D	0.553	neutral	None	None	None	None	I
K/L	0.3746	ambiguous	0.5293	ambiguous	0.421	Stabilizing	0.149	N	0.519	neutral	None	None	None	None	I
K/M	0.2508	likely_benign	0.3647	ambiguous	0.134	Stabilizing	0.915	D	0.509	neutral	N	0.517309845	None	None	I
K/N	0.4002	ambiguous	0.5394	ambiguous	-0.197	Destabilizing	0.317	N	0.477	neutral	N	0.493672182	None	None	I
K/P	0.408	ambiguous	0.4858	ambiguous	0.16	Stabilizing	None	N	0.231	neutral	None	None	None	None	I
K/Q	0.1303	likely_benign	0.1815	benign	-0.241	Destabilizing	0.317	N	0.511	neutral	N	0.518975526	None	None	I
K/R	0.0829	likely_benign	0.0932	benign	-0.34	Destabilizing	None	N	0.195	neutral	N	0.505584941	None	None	I
K/S	0.431	ambiguous	0.5858	pathogenic	-0.866	Destabilizing	0.149	N	0.455	neutral	None	None	None	None	I
K/T	0.2226	likely_benign	0.3243	benign	-0.557	Destabilizing	0.117	N	0.489	neutral	N	0.484353338	None	None	I
K/V	0.3896	ambiguous	0.5463	ambiguous	0.16	Stabilizing	0.38	N	0.523	neutral	None	None	None	None	I
K/W	0.7007	likely_pathogenic	0.8544	pathogenic	-0.02	Destabilizing	0.935	D	0.632	neutral	None	None	None	None	I
K/Y	0.5404	ambiguous	0.7167	pathogenic	0.256	Stabilizing	0.555	D	0.562	neutral	None	None	None	None	I

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.