TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2505	7738;7739;7740	chr2:178773543;178773542;178773541	chr2:179638270;179638269;179638268
N2AB	2505	7738;7739;7740	chr2:178773543;178773542;178773541	chr2:179638270;179638269;179638268
N2A	2505	7738;7739;7740	chr2:178773543;178773542;178773541	chr2:179638270;179638269;179638268
N2B	2459	7600;7601;7602	chr2:178773543;178773542;178773541	chr2:179638270;179638269;179638268
Novex-1	2459	7600;7601;7602	chr2:178773543;178773542;178773541	chr2:179638270;179638269;179638268
Novex-2	2459	7600;7601;7602	chr2:178773543;178773542;178773541	chr2:179638270;179638269;179638268
Novex-3	2505	7738;7739;7740	chr2:178773543;178773542;178773541	chr2:179638270;179638269;179638268

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-14
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.3558
• 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/K	None	None	0.801	N	0.347	0.15	0.146414634003	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/Y	None	None	0.989	N	0.511	0.412	0.620613072855	gnomAD-4.0.0	1.59068E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85677E-06	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
N/A	0.2396	likely_benign	0.2049	benign	-0.739	Destabilizing	0.525	D	0.404	neutral	None	None	None	None	N
N/C	0.2752	likely_benign	0.2467	benign	-0.053	Destabilizing	0.998	D	0.512	neutral	None	None	None	None	N
N/D	0.2667	likely_benign	0.2192	benign	-0.816	Destabilizing	0.801	D	0.397	neutral	N	0.497897518	None	None	N
N/E	0.514	ambiguous	0.4235	ambiguous	-0.732	Destabilizing	0.842	D	0.349	neutral	None	None	None	None	N
N/F	0.4875	ambiguous	0.437	ambiguous	-0.469	Destabilizing	0.974	D	0.555	neutral	None	None	None	None	N
N/G	0.2567	likely_benign	0.2328	benign	-1.069	Destabilizing	0.525	D	0.342	neutral	None	None	None	None	N
N/H	0.1029	likely_benign	0.097	benign	-0.826	Destabilizing	0.989	D	0.399	neutral	N	0.501629175	None	None	N
N/I	0.2547	likely_benign	0.215	benign	0.093	Stabilizing	0.934	D	0.508	neutral	N	0.513893785	None	None	N
N/K	0.3514	ambiguous	0.2864	benign	-0.401	Destabilizing	0.801	D	0.347	neutral	N	0.456279196	None	None	N
N/L	0.2155	likely_benign	0.1855	benign	0.093	Stabilizing	0.728	D	0.46	neutral	None	None	None	None	N
N/M	0.3422	ambiguous	0.2993	benign	0.519	Stabilizing	0.998	D	0.479	neutral	None	None	None	None	N
N/P	0.4928	ambiguous	0.4561	ambiguous	-0.155	Destabilizing	0.974	D	0.461	neutral	None	None	None	None	N
N/Q	0.3435	ambiguous	0.2989	benign	-1.028	Destabilizing	0.974	D	0.367	neutral	None	None	None	None	N
N/R	0.3704	ambiguous	0.316	benign	-0.371	Destabilizing	0.842	D	0.365	neutral	None	None	None	None	N
N/S	0.0775	likely_benign	0.0713	benign	-0.958	Destabilizing	0.022	N	0.09	neutral	N	0.442612209	None	None	N
N/T	0.106	likely_benign	0.0934	benign	-0.699	Destabilizing	0.022	N	0.079	neutral	N	0.444137673	None	None	N
N/V	0.2906	likely_benign	0.2403	benign	-0.155	Destabilizing	0.728	D	0.475	neutral	None	None	None	None	N
N/W	0.7456	likely_pathogenic	0.7076	pathogenic	-0.254	Destabilizing	0.998	D	0.596	neutral	None	None	None	None	N
N/Y	0.161	likely_benign	0.1418	benign	-0.048	Destabilizing	0.989	D	0.511	neutral	N	0.510760964	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.