TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20263	61012;61013;61014	chr2:178590938;178590937;178590936	chr2:179455665;179455664;179455663
N2AB	18622	56089;56090;56091	chr2:178590938;178590937;178590936	chr2:179455665;179455664;179455663
N2A	17695	53308;53309;53310	chr2:178590938;178590937;178590936	chr2:179455665;179455664;179455663
N2B	11198	33817;33818;33819	chr2:178590938;178590937;178590936	chr2:179455665;179455664;179455663
Novex-1	11323	34192;34193;34194	chr2:178590938;178590937;178590936	chr2:179455665;179455664;179455663
Novex-2	11390	34393;34394;34395	chr2:178590938;178590937;178590936	chr2:179455665;179455664;179455663
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-34
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.5004
• 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	rs886038850	-0.441	0.058	N	0.314	0.167	0.112648838833	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
T/A	rs886038850	-0.441	0.058	N	0.314	0.167	0.112648838833	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93874E-04	None	0	0	0	0	0
T/A	rs886038850	-0.441	0.058	N	0.314	0.167	0.112648838833	gnomAD-4.0.0	1.85968E-06	None	None	None	None	N	None	0	0	None	0	4.46229E-05	None	0	0	8.47836E-07	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	0.0841	likely_benign	0.0862	benign	-0.819	Destabilizing	0.058	N	0.314	neutral	N	0.511819401	None	None	N
T/C	0.3308	likely_benign	0.3189	benign	-0.564	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
T/D	0.6946	likely_pathogenic	0.7197	pathogenic	-0.384	Destabilizing	0.995	D	0.725	deleterious	None	None	None	None	N
T/E	0.3833	ambiguous	0.3951	ambiguous	-0.274	Destabilizing	0.989	D	0.674	prob.neutral	None	None	None	None	N
T/F	0.3206	likely_benign	0.3145	benign	-0.677	Destabilizing	0.995	D	0.855	deleterious	None	None	None	None	N
T/G	0.4629	ambiguous	0.4697	ambiguous	-1.173	Destabilizing	0.929	D	0.679	prob.neutral	None	None	None	None	N
T/H	0.3884	ambiguous	0.3884	ambiguous	-1.271	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
T/I	0.1307	likely_benign	0.131	benign	0.063	Stabilizing	0.986	D	0.743	deleterious	N	0.375214391	None	None	N
T/K	0.3203	likely_benign	0.3072	benign	-0.543	Destabilizing	0.989	D	0.649	prob.neutral	None	None	None	None	N
T/L	0.1225	likely_benign	0.122	benign	0.063	Stabilizing	0.963	D	0.636	neutral	None	None	None	None	N
T/M	0.0894	likely_benign	0.0902	benign	0.046	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
T/N	0.336	likely_benign	0.3675	ambiguous	-0.886	Destabilizing	0.993	D	0.648	neutral	N	0.513206268	None	None	N
T/P	0.7108	likely_pathogenic	0.7249	pathogenic	-0.197	Destabilizing	0.993	D	0.754	deleterious	N	0.494351148	None	None	N
T/Q	0.2868	likely_benign	0.2847	benign	-0.784	Destabilizing	0.995	D	0.743	deleterious	None	None	None	None	N
T/R	0.2527	likely_benign	0.2454	benign	-0.533	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
T/S	0.1898	likely_benign	0.1983	benign	-1.18	Destabilizing	0.908	D	0.505	neutral	N	0.492270848	None	None	N
T/V	0.0895	likely_benign	0.0868	benign	-0.197	Destabilizing	0.929	D	0.504	neutral	None	None	None	None	N
T/W	0.7274	likely_pathogenic	0.7151	pathogenic	-0.736	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
T/Y	0.3869	ambiguous	0.3856	ambiguous	-0.413	Destabilizing	0.998	D	0.847	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.