TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1646	5161;5162;5163	chr2:178776928;178776927;178776926	chr2:179641655;179641654;179641653
N2AB	1646	5161;5162;5163	chr2:178776928;178776927;178776926	chr2:179641655;179641654;179641653
N2A	1646	5161;5162;5163	chr2:178776928;178776927;178776926	chr2:179641655;179641654;179641653
N2B	1600	5023;5024;5025	chr2:178776928;178776927;178776926	chr2:179641655;179641654;179641653
Novex-1	1600	5023;5024;5025	chr2:178776928;178776927;178776926	chr2:179641655;179641654;179641653
Novex-2	1600	5023;5024;5025	chr2:178776928;178776927;178776926	chr2:179641655;179641654;179641653
Novex-3	1646	5161;5162;5163	chr2:178776928;178776927;178776926	chr2:179641655;179641654;179641653

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-7
• Domain position: 91
• Structural Position: 175
• Q(SASA): 0.3352
• 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/S	rs2092286263	None	0.999	N	0.584	0.372	0.44711355012	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85909E-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	0.4637	ambiguous	0.4134	ambiguous	-0.637	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
N/C	0.6426	likely_pathogenic	0.5642	pathogenic	0.056	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
N/D	0.5653	likely_pathogenic	0.5406	ambiguous	-0.924	Destabilizing	0.999	D	0.617	neutral	N	0.500223409	None	None	N
N/E	0.8517	likely_pathogenic	0.8285	pathogenic	-0.866	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
N/F	0.7201	likely_pathogenic	0.6863	pathogenic	-0.584	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
N/G	0.622	likely_pathogenic	0.586	pathogenic	-0.935	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
N/H	0.214	likely_benign	0.1994	benign	-0.839	Destabilizing	1.0	D	0.743	deleterious	N	0.512271871	None	None	N
N/I	0.3387	likely_benign	0.3139	benign	0.101	Stabilizing	1.0	D	0.819	deleterious	N	0.495606551	None	None	N
N/K	0.8018	likely_pathogenic	0.7781	pathogenic	-0.261	Destabilizing	1.0	D	0.739	prob.delet.	N	0.498942996	None	None	N
N/L	0.4091	ambiguous	0.3716	ambiguous	0.101	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
N/M	0.4525	ambiguous	0.403	ambiguous	0.65	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/P	0.9772	likely_pathogenic	0.9686	pathogenic	-0.115	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
N/Q	0.6907	likely_pathogenic	0.6473	pathogenic	-0.982	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
N/R	0.7867	likely_pathogenic	0.7677	pathogenic	-0.192	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
N/S	0.1323	likely_benign	0.1286	benign	-0.771	Destabilizing	0.999	D	0.584	neutral	N	0.5090233	None	None	N
N/T	0.1973	likely_benign	0.179	benign	-0.546	Destabilizing	0.999	D	0.721	prob.delet.	N	0.465769479	None	None	N
N/V	0.3715	ambiguous	0.3367	benign	-0.115	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
N/W	0.9356	likely_pathogenic	0.9208	pathogenic	-0.406	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
N/Y	0.3938	ambiguous	0.3643	ambiguous	-0.164	Destabilizing	1.0	D	0.801	deleterious	N	0.511406596	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.