TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27973	84142;84143;84144	chr2:178562215;178562214;178562213	chr2:179426942;179426941;179426940
N2AB	26332	79219;79220;79221	chr2:178562215;178562214;178562213	chr2:179426942;179426941;179426940
N2A	25405	76438;76439;76440	chr2:178562215;178562214;178562213	chr2:179426942;179426941;179426940
N2B	18908	56947;56948;56949	chr2:178562215;178562214;178562213	chr2:179426942;179426941;179426940
Novex-1	19033	57322;57323;57324	chr2:178562215;178562214;178562213	chr2:179426942;179426941;179426940
Novex-2	19100	57523;57524;57525	chr2:178562215;178562214;178562213	chr2:179426942;179426941;179426940
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-142
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.588
• Predicted PPI site: I

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	None	N	0.163	0.148	0.0297737177859	gnomAD-4.0.0	6.8475E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9979E-07	0	0
N/S	None	None	None	N	0.111	0.072	0.0954503805726	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2374	likely_benign	0.2484	benign	-0.464	Destabilizing	0.007	N	0.203	neutral	None	None	None	None	I
N/C	0.2054	likely_benign	0.1959	benign	0.138	Stabilizing	0.676	D	0.301	neutral	None	None	None	None	I
N/D	0.2986	likely_benign	0.3461	ambiguous	0.363	Stabilizing	0.012	N	0.22	neutral	N	0.497386746	None	None	I
N/E	0.602	likely_pathogenic	0.6797	pathogenic	0.407	Stabilizing	0.016	N	0.199	neutral	None	None	None	None	I
N/F	0.5157	ambiguous	0.554	ambiguous	-0.541	Destabilizing	0.356	N	0.379	neutral	None	None	None	None	I
N/G	0.379	ambiguous	0.3827	ambiguous	-0.723	Destabilizing	0.016	N	0.189	neutral	None	None	None	None	I
N/H	0.0878	likely_benign	0.0959	benign	-0.466	Destabilizing	None	N	0.147	neutral	N	0.484342877	None	None	I
N/I	0.2117	likely_benign	0.2488	benign	0.153	Stabilizing	0.055	N	0.409	neutral	N	0.413866859	None	None	I
N/K	0.5332	ambiguous	0.6307	pathogenic	0.16	Stabilizing	None	N	0.163	neutral	N	0.460983228	None	None	I
N/L	0.2077	likely_benign	0.2435	benign	0.153	Stabilizing	0.016	N	0.303	neutral	None	None	None	None	I
N/M	0.3363	likely_benign	0.3609	ambiguous	0.258	Stabilizing	0.628	D	0.301	neutral	None	None	None	None	I
N/P	0.5396	ambiguous	0.5901	pathogenic	-0.023	Destabilizing	0.072	N	0.393	neutral	None	None	None	None	I
N/Q	0.4178	ambiguous	0.4694	ambiguous	-0.349	Destabilizing	0.072	N	0.178	neutral	None	None	None	None	I
N/R	0.4979	ambiguous	0.5869	pathogenic	0.153	Stabilizing	0.038	N	0.165	neutral	None	None	None	None	I
N/S	0.0634	likely_benign	0.0608	benign	-0.384	Destabilizing	None	N	0.111	neutral	N	0.392355436	None	None	I
N/T	0.0856	likely_benign	0.0928	benign	-0.156	Destabilizing	None	N	0.167	neutral	N	0.387352261	None	None	I
N/V	0.2067	likely_benign	0.2367	benign	-0.023	Destabilizing	0.038	N	0.361	neutral	None	None	None	None	I
N/W	0.7882	likely_pathogenic	0.8005	pathogenic	-0.418	Destabilizing	0.864	D	0.316	neutral	None	None	None	None	I
N/Y	0.149	likely_benign	0.1659	benign	-0.153	Destabilizing	0.093	N	0.388	neutral	N	0.484516236	None	None	I

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.