TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29544	88855;88856;88857	chr2:178554717;178554716;178554715	chr2:179419444;179419443;179419442
N2AB	27903	83932;83933;83934	chr2:178554717;178554716;178554715	chr2:179419444;179419443;179419442
N2A	26976	81151;81152;81153	chr2:178554717;178554716;178554715	chr2:179419444;179419443;179419442
N2B	20479	61660;61661;61662	chr2:178554717;178554716;178554715	chr2:179419444;179419443;179419442
Novex-1	20604	62035;62036;62037	chr2:178554717;178554716;178554715	chr2:179419444;179419443;179419442
Novex-2	20671	62236;62237;62238	chr2:178554717;178554716;178554715	chr2:179419444;179419443;179419442
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: Fn3-103
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.6095
• 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/R	None	None	0.014	N	0.194	0.065	0.151104730317	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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	0.63	likely_pathogenic	0.6073	pathogenic	-0.007	Destabilizing	0.86	D	0.579	neutral	None	None	None	None	N
K/C	0.7967	likely_pathogenic	0.7961	pathogenic	-0.292	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
K/D	0.8757	likely_pathogenic	0.8698	pathogenic	0.105	Stabilizing	0.978	D	0.662	neutral	None	None	None	None	N
K/E	0.4248	ambiguous	0.3838	ambiguous	0.116	Stabilizing	0.822	D	0.523	neutral	N	0.436113708	None	None	N
K/F	0.9175	likely_pathogenic	0.9207	pathogenic	-0.268	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
K/G	0.7474	likely_pathogenic	0.751	pathogenic	-0.194	Destabilizing	0.956	D	0.573	neutral	None	None	None	None	N
K/H	0.4289	ambiguous	0.4221	ambiguous	-0.443	Destabilizing	0.994	D	0.655	neutral	None	None	None	None	N
K/I	0.5998	likely_pathogenic	0.5845	pathogenic	0.405	Stabilizing	0.978	D	0.725	prob.delet.	None	None	None	None	N
K/L	0.5359	ambiguous	0.5346	ambiguous	0.405	Stabilizing	0.956	D	0.573	neutral	None	None	None	None	N
K/M	0.4363	ambiguous	0.4287	ambiguous	0.159	Stabilizing	0.997	D	0.649	neutral	N	0.485523808	None	None	N
K/N	0.7379	likely_pathogenic	0.7236	pathogenic	0.175	Stabilizing	0.942	D	0.596	neutral	N	0.47844312	None	None	N
K/P	0.9422	likely_pathogenic	0.9394	pathogenic	0.295	Stabilizing	0.993	D	0.684	prob.neutral	None	None	None	None	N
K/Q	0.1838	likely_benign	0.1786	benign	0.034	Stabilizing	0.942	D	0.591	neutral	N	0.452045953	None	None	N
K/R	0.0889	likely_benign	0.0961	benign	-0.011	Destabilizing	0.014	N	0.194	neutral	N	0.480712634	None	None	N
K/S	0.6735	likely_pathogenic	0.6521	pathogenic	-0.311	Destabilizing	0.86	D	0.59	neutral	None	None	None	None	N
K/T	0.3467	ambiguous	0.3177	benign	-0.148	Destabilizing	0.942	D	0.624	neutral	N	0.41156198	None	None	N
K/V	0.55	ambiguous	0.5282	ambiguous	0.295	Stabilizing	0.978	D	0.669	neutral	None	None	None	None	N
K/W	0.8841	likely_pathogenic	0.9048	pathogenic	-0.304	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
K/Y	0.8105	likely_pathogenic	0.8173	pathogenic	0.067	Stabilizing	0.993	D	0.685	prob.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.