TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6300	19123;19124;19125	chr2:178729140;178729139;178729138	chr2:179593867;179593866;179593865
N2AB	5983	18172;18173;18174	chr2:178729140;178729139;178729138	chr2:179593867;179593866;179593865
N2A	5056	15391;15392;15393	chr2:178729140;178729139;178729138	chr2:179593867;179593866;179593865
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-47
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4064
• 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	None	None	0.996	N	0.343	0.242	0.146414634003	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.7042	likely_pathogenic	0.6872	pathogenic	-0.369	Destabilizing	0.997	D	0.545	neutral	None	None	None	None	N
N/C	0.8753	likely_pathogenic	0.8819	pathogenic	0.272	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
N/D	0.2103	likely_benign	0.226	benign	0.291	Stabilizing	0.996	D	0.378	neutral	N	0.40358471	None	None	N
N/E	0.7575	likely_pathogenic	0.7505	pathogenic	0.272	Stabilizing	0.994	D	0.376	neutral	None	None	None	None	N
N/F	0.942	likely_pathogenic	0.9324	pathogenic	-0.675	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
N/G	0.6678	likely_pathogenic	0.6698	pathogenic	-0.56	Destabilizing	0.998	D	0.355	neutral	None	None	None	None	N
N/H	0.4498	ambiguous	0.4479	ambiguous	-0.507	Destabilizing	0.999	D	0.591	neutral	N	0.478951384	None	None	N
N/I	0.7752	likely_pathogenic	0.7468	pathogenic	0.052	Stabilizing	1.0	D	0.739	prob.delet.	N	0.496802149	None	None	N
N/K	0.8012	likely_pathogenic	0.7871	pathogenic	0.139	Stabilizing	0.992	D	0.449	neutral	N	0.489204826	None	None	N
N/L	0.7847	likely_pathogenic	0.7572	pathogenic	0.052	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
N/M	0.7821	likely_pathogenic	0.7597	pathogenic	0.292	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
N/P	0.8019	likely_pathogenic	0.785	pathogenic	-0.061	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
N/Q	0.8099	likely_pathogenic	0.7923	pathogenic	-0.327	Destabilizing	0.967	D	0.271	neutral	None	None	None	None	N
N/R	0.8653	likely_pathogenic	0.8555	pathogenic	0.173	Stabilizing	0.999	D	0.581	neutral	None	None	None	None	N
N/S	0.2637	likely_benign	0.2718	benign	-0.175	Destabilizing	0.996	D	0.343	neutral	N	0.473119366	None	None	N
N/T	0.4704	ambiguous	0.4523	ambiguous	-0.037	Destabilizing	0.998	D	0.492	neutral	N	0.461047712	None	None	N
N/V	0.7846	likely_pathogenic	0.759	pathogenic	-0.061	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
N/W	0.9769	likely_pathogenic	0.9727	pathogenic	-0.63	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
N/Y	0.5364	ambiguous	0.5067	ambiguous	-0.365	Destabilizing	1.0	D	0.711	prob.delet.	N	0.485699333	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.