TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13767	41524;41525;41526	chr2:178636428;178636427;178636426	chr2:179501155;179501154;179501153
N2AB	12126	36601;36602;36603	chr2:178636428;178636427;178636426	chr2:179501155;179501154;179501153
N2A	11199	33820;33821;33822	chr2:178636428;178636427;178636426	chr2:179501155;179501154;179501153
N2B	4702	14329;14330;14331	chr2:178636428;178636427;178636426	chr2:179501155;179501154;179501153
Novex-1	4827	14704;14705;14706	chr2:178636428;178636427;178636426	chr2:179501155;179501154;179501153
Novex-2	4894	14905;14906;14907	chr2:178636428;178636427;178636426	chr2:179501155;179501154;179501153
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-87
• Domain position: 84
• Structural Position: 166
• Q(SASA): 0.3284
• 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/N	None	None	0.999	N	0.667	0.284	0.258283824007	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.8203	likely_pathogenic	0.8931	pathogenic	-0.293	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	N
K/C	0.9597	likely_pathogenic	0.9724	pathogenic	-0.495	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/D	0.968	likely_pathogenic	0.9835	pathogenic	0.072	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/E	0.78	likely_pathogenic	0.884	pathogenic	0.163	Stabilizing	0.998	D	0.597	neutral	N	0.476128292	None	None	N
K/F	0.9728	likely_pathogenic	0.9846	pathogenic	-0.118	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
K/G	0.9439	likely_pathogenic	0.9631	pathogenic	-0.598	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/H	0.7507	likely_pathogenic	0.8298	pathogenic	-0.748	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/I	0.6753	likely_pathogenic	0.7956	pathogenic	0.47	Stabilizing	0.611	D	0.595	neutral	None	None	None	None	N
K/L	0.7876	likely_pathogenic	0.8546	pathogenic	0.47	Stabilizing	0.96	D	0.669	neutral	None	None	None	None	N
K/M	0.5564	ambiguous	0.6881	pathogenic	0.037	Stabilizing	0.998	D	0.72	prob.delet.	N	0.51348892	None	None	N
K/N	0.8973	likely_pathogenic	0.9476	pathogenic	-0.217	Destabilizing	0.999	D	0.667	neutral	N	0.493184907	None	None	N
K/P	0.9972	likely_pathogenic	0.9978	pathogenic	0.245	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/Q	0.4458	ambiguous	0.5939	pathogenic	-0.236	Destabilizing	0.999	D	0.664	neutral	N	0.485273993	None	None	N
K/R	0.1896	likely_benign	0.2127	benign	-0.281	Destabilizing	0.998	D	0.606	neutral	N	0.467998358	None	None	N
K/S	0.9191	likely_pathogenic	0.9617	pathogenic	-0.766	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
K/T	0.5352	ambiguous	0.7483	pathogenic	-0.483	Destabilizing	0.998	D	0.726	prob.delet.	N	0.466977098	None	None	N
K/V	0.6296	likely_pathogenic	0.7473	pathogenic	0.245	Stabilizing	0.983	D	0.688	prob.neutral	None	None	None	None	N
K/W	0.9783	likely_pathogenic	0.9863	pathogenic	-0.087	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/Y	0.9344	likely_pathogenic	0.9579	pathogenic	0.219	Stabilizing	1.0	D	0.769	deleterious	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.