TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27535	82828;82829;82830	chr2:178563529;178563528;178563527	chr2:179428256;179428255;179428254
N2AB	25894	77905;77906;77907	chr2:178563529;178563528;178563527	chr2:179428256;179428255;179428254
N2A	24967	75124;75125;75126	chr2:178563529;178563528;178563527	chr2:179428256;179428255;179428254
N2B	18470	55633;55634;55635	chr2:178563529;178563528;178563527	chr2:179428256;179428255;179428254
Novex-1	18595	56008;56009;56010	chr2:178563529;178563528;178563527	chr2:179428256;179428255;179428254
Novex-2	18662	56209;56210;56211	chr2:178563529;178563528;178563527	chr2:179428256;179428255;179428254
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-88
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.386
• 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/A	rs775733174	-0.978	0.822	N	0.437	0.185	0.239901079897	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
T/A	rs775733174	-0.978	0.822	N	0.437	0.185	0.239901079897	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99471E-07	1.15934E-05	0
T/I	None	None	0.89	N	0.509	0.258	0.325533332567	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
T/A	0.0861	likely_benign	0.0869	benign	-0.895	Destabilizing	0.822	D	0.437	neutral	N	0.490044194	None	None	N
T/C	0.3866	ambiguous	0.4037	ambiguous	-0.423	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	N
T/D	0.6291	likely_pathogenic	0.6241	pathogenic	-0.177	Destabilizing	0.993	D	0.581	neutral	None	None	None	None	N
T/E	0.4331	ambiguous	0.4412	ambiguous	-0.168	Destabilizing	0.978	D	0.531	neutral	None	None	None	None	N
T/F	0.2636	likely_benign	0.2729	benign	-0.933	Destabilizing	0.915	D	0.595	neutral	None	None	None	None	N
T/G	0.2676	likely_benign	0.2779	benign	-1.164	Destabilizing	0.978	D	0.533	neutral	None	None	None	None	N
T/H	0.3103	likely_benign	0.3126	benign	-1.323	Destabilizing	0.988	D	0.651	neutral	None	None	None	None	N
T/I	0.118	likely_benign	0.1188	benign	-0.266	Destabilizing	0.89	D	0.509	neutral	N	0.460300077	None	None	N
T/K	0.2804	likely_benign	0.2801	benign	-0.739	Destabilizing	0.978	D	0.528	neutral	None	None	None	None	N
T/L	0.0658	likely_benign	0.0705	benign	-0.266	Destabilizing	0.559	D	0.465	neutral	None	None	None	None	N
T/M	0.0721	likely_benign	0.0724	benign	-0.013	Destabilizing	0.559	D	0.359	neutral	None	None	None	None	N
T/N	0.1621	likely_benign	0.1588	benign	-0.656	Destabilizing	0.97	D	0.531	neutral	N	0.508168595	None	None	N
T/P	0.2197	likely_benign	0.2571	benign	-0.444	Destabilizing	0.99	D	0.588	neutral	D	0.523407406	None	None	N
T/Q	0.2452	likely_benign	0.2443	benign	-0.769	Destabilizing	0.978	D	0.589	neutral	None	None	None	None	N
T/R	0.2301	likely_benign	0.2343	benign	-0.483	Destabilizing	0.978	D	0.585	neutral	None	None	None	None	N
T/S	0.1248	likely_benign	0.1334	benign	-0.948	Destabilizing	0.904	D	0.436	neutral	N	0.457451773	None	None	N
T/V	0.0971	likely_benign	0.0953	benign	-0.444	Destabilizing	0.754	D	0.42	neutral	None	None	None	None	N
T/W	0.5633	ambiguous	0.5963	pathogenic	-0.885	Destabilizing	0.994	D	0.647	neutral	None	None	None	None	N
T/Y	0.3483	ambiguous	0.3619	ambiguous	-0.666	Destabilizing	0.043	N	0.309	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.