TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15276	46051;46052;46053	chr2:178620784;178620783;178620782	chr2:179485511;179485510;179485509
N2AB	13635	41128;41129;41130	chr2:178620784;178620783;178620782	chr2:179485511;179485510;179485509
N2A	12708	38347;38348;38349	chr2:178620784;178620783;178620782	chr2:179485511;179485510;179485509
N2B	6211	18856;18857;18858	chr2:178620784;178620783;178620782	chr2:179485511;179485510;179485509
Novex-1	6336	19231;19232;19233	chr2:178620784;178620783;178620782	chr2:179485511;179485510;179485509
Novex-2	6403	19432;19433;19434	chr2:178620784;178620783;178620782	chr2:179485511;179485510;179485509
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-104
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.4278
• 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/H	None	None	0.912	N	0.561	0.182	0.366277470483	gnomAD-4.0.0	1.59329E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86261E-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	0.1316	likely_benign	0.1613	benign	-0.757	Destabilizing	0.116	N	0.519	neutral	None	None	None	None	N
N/C	0.1924	likely_benign	0.2263	benign	-0.013	Destabilizing	0.944	D	0.598	neutral	None	None	None	None	N
N/D	0.1146	likely_benign	0.1256	benign	-1.373	Destabilizing	0.09	N	0.554	neutral	N	0.500841304	None	None	N
N/E	0.2601	likely_benign	0.3234	benign	-1.249	Destabilizing	0.008	N	0.223	neutral	None	None	None	None	N
N/F	0.349	ambiguous	0.405	ambiguous	-0.568	Destabilizing	0.818	D	0.607	neutral	None	None	None	None	N
N/G	0.2218	likely_benign	0.2769	benign	-1.118	Destabilizing	0.207	N	0.525	neutral	None	None	None	None	N
N/H	0.0885	likely_benign	0.1004	benign	-0.976	Destabilizing	0.912	D	0.561	neutral	N	0.497454077	None	None	N
N/I	0.1165	likely_benign	0.1275	benign	0.169	Stabilizing	0.457	N	0.616	neutral	N	0.479683748	None	None	N
N/K	0.1522	likely_benign	0.202	benign	-0.306	Destabilizing	0.324	N	0.521	neutral	N	0.486978154	None	None	N
N/L	0.1604	likely_benign	0.1847	benign	0.169	Stabilizing	0.241	N	0.547	neutral	None	None	None	None	N
N/M	0.235	likely_benign	0.2751	benign	0.728	Stabilizing	0.944	D	0.589	neutral	None	None	None	None	N
N/P	0.4063	ambiguous	0.4723	ambiguous	-0.109	Destabilizing	0.818	D	0.601	neutral	None	None	None	None	N
N/Q	0.2102	likely_benign	0.2764	benign	-1.059	Destabilizing	0.69	D	0.537	neutral	None	None	None	None	N
N/R	0.1624	likely_benign	0.2182	benign	-0.362	Destabilizing	0.388	N	0.52	neutral	None	None	None	None	N
N/S	0.0658	likely_benign	0.0727	benign	-1.003	Destabilizing	0.09	N	0.545	neutral	N	0.471462844	None	None	N
N/T	0.0848	likely_benign	0.0948	benign	-0.694	Destabilizing	0.001	N	0.175	neutral	N	0.427976954	None	None	N
N/V	0.1287	likely_benign	0.145	benign	-0.109	Destabilizing	0.241	N	0.561	neutral	None	None	None	None	N
N/W	0.6443	likely_pathogenic	0.7106	pathogenic	-0.43	Destabilizing	0.981	D	0.627	neutral	None	None	None	None	N
N/Y	0.1264	likely_benign	0.1358	benign	-0.142	Destabilizing	0.773	D	0.613	neutral	D	0.531036961	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.