TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22567	67924;67925;67926	chr2:178579331;178579330;178579329	chr2:179444058;179444057;179444056
N2AB	20926	63001;63002;63003	chr2:178579331;178579330;178579329	chr2:179444058;179444057;179444056
N2A	19999	60220;60221;60222	chr2:178579331;178579330;178579329	chr2:179444058;179444057;179444056
N2B	13502	40729;40730;40731	chr2:178579331;178579330;178579329	chr2:179444058;179444057;179444056
Novex-1	13627	41104;41105;41106	chr2:178579331;178579330;178579329	chr2:179444058;179444057;179444056
Novex-2	13694	41305;41306;41307	chr2:178579331;178579330;178579329	chr2:179444058;179444057;179444056
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-127
• Domain position: 8
• Structural Position: 26
• Q(SASA): 0.5266
• 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
N/D	rs2047147885	None	0.425	N	0.233	0.168	0.110078149338	gnomAD-4.0.0	6.43318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.1548E-05	0	0
N/S	None	None	0.003	N	0.149	0.073	0.0986583533028	gnomAD-4.0.0	1.37442E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0221E-07	0	1.66406E-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
N/A	0.2898	likely_benign	0.2602	benign	-0.754	Destabilizing	0.176	N	0.249	neutral	None	None	None	None	N
N/C	0.3567	ambiguous	0.3542	ambiguous	0.199	Stabilizing	0.007	N	0.268	neutral	None	None	None	None	N
N/D	0.291	likely_benign	0.2305	benign	0.067	Stabilizing	0.425	N	0.233	neutral	N	0.406337014	None	None	N
N/E	0.7281	likely_pathogenic	0.6583	pathogenic	0.085	Stabilizing	0.495	N	0.211	neutral	None	None	None	None	N
N/F	0.7371	likely_pathogenic	0.6867	pathogenic	-0.895	Destabilizing	0.981	D	0.387	neutral	None	None	None	None	N
N/G	0.3723	ambiguous	0.3367	benign	-0.998	Destabilizing	0.329	N	0.277	neutral	None	None	None	None	N
N/H	0.1837	likely_benign	0.1656	benign	-0.874	Destabilizing	0.975	D	0.307	neutral	N	0.477989255	None	None	N
N/I	0.3945	ambiguous	0.3489	ambiguous	-0.174	Destabilizing	0.642	D	0.421	neutral	N	0.496575016	None	None	N
N/K	0.6205	likely_pathogenic	0.5297	ambiguous	-0.063	Destabilizing	0.425	N	0.212	neutral	N	0.428560513	None	None	N
N/L	0.3745	ambiguous	0.3419	ambiguous	-0.174	Destabilizing	0.329	N	0.386	neutral	None	None	None	None	N
N/M	0.5383	ambiguous	0.4999	ambiguous	0.265	Stabilizing	0.981	D	0.339	neutral	None	None	None	None	N
N/P	0.391	ambiguous	0.3317	benign	-0.34	Destabilizing	0.828	D	0.397	neutral	None	None	None	None	N
N/Q	0.5563	ambiguous	0.502	ambiguous	-0.554	Destabilizing	0.828	D	0.251	neutral	None	None	None	None	N
N/R	0.571	likely_pathogenic	0.4957	ambiguous	-0.024	Destabilizing	0.704	D	0.212	neutral	None	None	None	None	N
N/S	0.0813	likely_benign	0.0785	benign	-0.476	Destabilizing	0.003	N	0.149	neutral	N	0.420284959	None	None	N
N/T	0.1611	likely_benign	0.1422	benign	-0.282	Destabilizing	0.003	N	0.147	neutral	N	0.366855906	None	None	N
N/V	0.3398	likely_benign	0.309	benign	-0.34	Destabilizing	0.495	N	0.379	neutral	None	None	None	None	N
N/W	0.8986	likely_pathogenic	0.8862	pathogenic	-0.748	Destabilizing	0.995	D	0.362	neutral	None	None	None	None	N
N/Y	0.3045	likely_benign	0.2638	benign	-0.539	Destabilizing	0.975	D	0.363	neutral	N	0.496748374	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.