TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19438	58537;58538;58539	chr2:178594081;178594080;178594079	chr2:179458808;179458807;179458806
N2AB	17797	53614;53615;53616	chr2:178594081;178594080;178594079	chr2:179458808;179458807;179458806
N2A	16870	50833;50834;50835	chr2:178594081;178594080;178594079	chr2:179458808;179458807;179458806
N2B	10373	31342;31343;31344	chr2:178594081;178594080;178594079	chr2:179458808;179458807;179458806
Novex-1	10498	31717;31718;31719	chr2:178594081;178594080;178594079	chr2:179458808;179458807;179458806
Novex-2	10565	31918;31919;31920	chr2:178594081;178594080;178594079	chr2:179458808;179458807;179458806
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-118
• Domain position: 48
• Structural Position: 130
• Q(SASA): 0.3398
• 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
T/I	rs182907667	None	0.971	N	0.557	0.387	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94024E-04	None	0	0	0	0	0
T/I	rs182907667	None	0.971	N	0.557	0.387	None	gnomAD-4.0.0	6.57212E-06	None	None	None	None	N	None	0	0	None	0	1.94477E-04	None	0	0	0	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
T/A	0.1426	likely_benign	0.1463	benign	-0.449	Destabilizing	0.489	N	0.387	neutral	N	0.517186015	None	None	N
T/C	0.6381	likely_pathogenic	0.6504	pathogenic	-0.264	Destabilizing	0.998	D	0.58	neutral	None	None	None	None	N
T/D	0.423	ambiguous	0.4709	ambiguous	0.217	Stabilizing	0.956	D	0.487	neutral	None	None	None	None	N
T/E	0.4583	ambiguous	0.5109	ambiguous	0.166	Stabilizing	0.956	D	0.496	neutral	None	None	None	None	N
T/F	0.3741	ambiguous	0.4026	ambiguous	-0.824	Destabilizing	0.978	D	0.628	neutral	None	None	None	None	N
T/G	0.2135	likely_benign	0.2182	benign	-0.622	Destabilizing	0.754	D	0.476	neutral	None	None	None	None	N
T/H	0.4259	ambiguous	0.4451	ambiguous	-0.869	Destabilizing	0.994	D	0.628	neutral	None	None	None	None	N
T/I	0.3442	ambiguous	0.3868	ambiguous	-0.107	Destabilizing	0.971	D	0.557	neutral	N	0.491443682	None	None	N
T/K	0.3294	likely_benign	0.3972	ambiguous	-0.397	Destabilizing	0.89	D	0.49	neutral	N	0.519935531	None	None	N
T/L	0.1446	likely_benign	0.1571	benign	-0.107	Destabilizing	0.86	D	0.449	neutral	None	None	None	None	N
T/M	0.1408	likely_benign	0.1479	benign	0.028	Stabilizing	0.998	D	0.571	neutral	None	None	None	None	N
T/N	0.1518	likely_benign	0.1678	benign	-0.228	Destabilizing	0.915	D	0.45	neutral	None	None	None	None	N
T/P	0.438	ambiguous	0.5349	ambiguous	-0.19	Destabilizing	0.971	D	0.554	neutral	N	0.505433334	None	None	N
T/Q	0.3987	ambiguous	0.4288	ambiguous	-0.408	Destabilizing	0.956	D	0.558	neutral	None	None	None	None	N
T/R	0.3554	ambiguous	0.4114	ambiguous	-0.133	Destabilizing	0.942	D	0.553	neutral	N	0.492556091	None	None	N
T/S	0.1109	likely_benign	0.1121	benign	-0.466	Destabilizing	0.058	N	0.199	neutral	N	0.498541539	None	None	N
T/V	0.2583	likely_benign	0.2807	benign	-0.19	Destabilizing	0.86	D	0.389	neutral	None	None	None	None	N
T/W	0.8022	likely_pathogenic	0.8229	pathogenic	-0.823	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
T/Y	0.4515	ambiguous	0.4887	ambiguous	-0.548	Destabilizing	0.993	D	0.633	neutral	None	None	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.