TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32887	98884;98885;98886	chr2:178539406;178539405;178539404	chr2:179404133;179404132;179404131
N2AB	31246	93961;93962;93963	chr2:178539406;178539405;178539404	chr2:179404133;179404132;179404131
N2A	30319	91180;91181;91182	chr2:178539406;178539405;178539404	chr2:179404133;179404132;179404131
N2B	23822	71689;71690;71691	chr2:178539406;178539405;178539404	chr2:179404133;179404132;179404131
Novex-1	23947	72064;72065;72066	chr2:178539406;178539405;178539404	chr2:179404133;179404132;179404131
Novex-2	24014	72265;72266;72267	chr2:178539406;178539405;178539404	chr2:179404133;179404132;179404131
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-127
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.3044
• 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
P/A	rs55653324	-1.249	0.029	N	0.231	0.111	0.141422826196	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	1.96155E-04	None	0	0	1.65893E-04
P/A	rs55653324	-1.249	0.029	N	0.231	0.111	0.141422826196	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07297E-04	0
P/A	rs55653324	-1.249	0.029	N	0.231	0.111	0.141422826196	gnomAD-4.0.0	1.92236E-05	None	None	None	None	N	None	0	0	None	0	2.22955E-05	None	0	0	0	3.29439E-04	0
P/Q	rs774623766	-0.979	0.974	N	0.59	0.339	0.280987212366	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.56E-05	0
P/Q	rs774623766	-0.979	0.974	N	0.59	0.339	0.280987212366	gnomAD-4.0.0	6.84775E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00302E-07	0	0
P/R	None	None	0.974	N	0.685	0.377	0.313518423057	gnomAD-4.0.0	6.84775E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65755E-05
P/S	None	None	0.08	N	0.247	0.166	0.148003135375	gnomAD-4.0.0	1.36944E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73611E-04	0	1.15955E-05	0
P/T	rs55653324	None	0.728	N	0.537	0.185	0.202086224978	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs55653324	None	0.728	N	0.537	0.185	0.202086224978	gnomAD-4.0.0	6.57272E-06	None	None	None	None	N	None	2.41371E-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
P/A	0.0708	likely_benign	0.0696	benign	-1.362	Destabilizing	0.029	N	0.231	neutral	N	0.492937278	None	None	N
P/C	0.5402	ambiguous	0.4964	ambiguous	-0.756	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
P/D	0.7397	likely_pathogenic	0.7003	pathogenic	-1.111	Destabilizing	0.876	D	0.551	neutral	None	None	None	None	N
P/E	0.5535	ambiguous	0.5203	ambiguous	-1.141	Destabilizing	0.876	D	0.526	neutral	None	None	None	None	N
P/F	0.651	likely_pathogenic	0.6189	pathogenic	-1.134	Destabilizing	0.994	D	0.729	deleterious	None	None	None	None	N
P/G	0.377	ambiguous	0.3632	ambiguous	-1.653	Destabilizing	0.745	D	0.533	neutral	None	None	None	None	N
P/H	0.4172	ambiguous	0.3824	ambiguous	-1.159	Destabilizing	0.998	D	0.651	prob.neutral	None	None	None	None	N
P/I	0.3671	ambiguous	0.3438	ambiguous	-0.675	Destabilizing	0.981	D	0.742	deleterious	None	None	None	None	N
P/K	0.4949	ambiguous	0.4612	ambiguous	-1.073	Destabilizing	0.876	D	0.542	neutral	None	None	None	None	N
P/L	0.2341	likely_benign	0.1993	benign	-0.675	Destabilizing	0.842	D	0.674	prob.neutral	N	0.46069209	None	None	N
P/M	0.3917	ambiguous	0.3572	ambiguous	-0.412	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
P/N	0.5433	ambiguous	0.4976	ambiguous	-0.755	Destabilizing	0.961	D	0.687	prob.delet.	None	None	None	None	N
P/Q	0.3441	ambiguous	0.3132	benign	-0.966	Destabilizing	0.974	D	0.59	neutral	N	0.472670733	None	None	N
P/R	0.3463	ambiguous	0.3187	benign	-0.503	Destabilizing	0.974	D	0.685	prob.delet.	N	0.477595031	None	None	N
P/S	0.1761	likely_benign	0.1647	benign	-1.253	Destabilizing	0.08	N	0.247	neutral	N	0.461199069	None	None	N
P/T	0.1316	likely_benign	0.1192	benign	-1.176	Destabilizing	0.728	D	0.537	neutral	N	0.467578171	None	None	N
P/V	0.24	likely_benign	0.2268	benign	-0.869	Destabilizing	0.876	D	0.629	neutral	None	None	None	None	N
P/W	0.7965	likely_pathogenic	0.7779	pathogenic	-1.285	Destabilizing	0.998	D	0.731	deleterious	None	None	None	None	N
P/Y	0.6324	likely_pathogenic	0.6024	pathogenic	-1.014	Destabilizing	0.994	D	0.731	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.