TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9257	27994;27995;27996	chr2:178712061;178712060;178712059	chr2:179576788;179576787;179576786
N2AB	8940	27043;27044;27045	chr2:178712061;178712060;178712059	chr2:179576788;179576787;179576786
N2A	8013	24262;24263;24264	chr2:178712061;178712060;178712059	chr2:179576788;179576787;179576786
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-78
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.6747
• 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/S	rs1448296665	None	0.704	N	0.286	0.169	0.0954503805726	gnomAD-4.0.0	2.73685E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59792E-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	0.5345	ambiguous	0.5892	pathogenic	-0.061	Destabilizing	0.17	N	0.207	neutral	None	None	None	None	I
N/C	0.6247	likely_pathogenic	0.71	pathogenic	0.107	Stabilizing	0.999	D	0.243	neutral	None	None	None	None	I
N/D	0.1347	likely_benign	0.146	benign	0.278	Stabilizing	0.035	N	0.129	neutral	N	0.437331925	None	None	I
N/E	0.4956	ambiguous	0.5111	ambiguous	0.233	Stabilizing	0.759	D	0.225	neutral	None	None	None	None	I
N/F	0.8709	likely_pathogenic	0.8792	pathogenic	-0.639	Destabilizing	0.997	D	0.241	neutral	None	None	None	None	I
N/G	0.3415	ambiguous	0.3911	ambiguous	-0.173	Destabilizing	0.863	D	0.274	neutral	None	None	None	None	I
N/H	0.1868	likely_benign	0.2189	benign	-0.126	Destabilizing	0.996	D	0.221	neutral	N	0.455616435	None	None	I
N/I	0.7821	likely_pathogenic	0.8156	pathogenic	0.134	Stabilizing	0.988	D	0.277	neutral	N	0.465998463	None	None	I
N/K	0.4371	ambiguous	0.4617	ambiguous	0.178	Stabilizing	0.061	N	0.096	neutral	N	0.488454178	None	None	I
N/L	0.6572	likely_pathogenic	0.672	pathogenic	0.134	Stabilizing	0.939	D	0.305	neutral	None	None	None	None	I
N/M	0.6996	likely_pathogenic	0.7068	pathogenic	0.056	Stabilizing	0.999	D	0.215	neutral	None	None	None	None	I
N/P	0.9149	likely_pathogenic	0.9364	pathogenic	0.094	Stabilizing	0.991	D	0.271	neutral	None	None	None	None	I
N/Q	0.4584	ambiguous	0.4751	ambiguous	-0.227	Destabilizing	0.939	D	0.239	neutral	None	None	None	None	I
N/R	0.5055	ambiguous	0.5317	ambiguous	0.241	Stabilizing	0.884	D	0.185	neutral	None	None	None	None	I
N/S	0.1505	likely_benign	0.175	benign	-0.057	Destabilizing	0.704	D	0.286	neutral	N	0.50078597	None	None	I
N/T	0.4537	ambiguous	0.4775	ambiguous	0.024	Stabilizing	0.92	D	0.193	neutral	N	0.499113889	None	None	I
N/V	0.7685	likely_pathogenic	0.8056	pathogenic	0.094	Stabilizing	0.939	D	0.335	neutral	None	None	None	None	I
N/W	0.8905	likely_pathogenic	0.9199	pathogenic	-0.772	Destabilizing	0.999	D	0.375	neutral	None	None	None	None	I
N/Y	0.3392	likely_benign	0.3702	ambiguous	-0.429	Destabilizing	0.996	D	0.223	neutral	N	0.469125561	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.