TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8725	26398;26399;26400	chr2:178715013;178715012;178715011	chr2:179579740;179579739;179579738
N2AB	8408	25447;25448;25449	chr2:178715013;178715012;178715011	chr2:179579740;179579739;179579738
N2A	7481	22666;22667;22668	chr2:178715013;178715012;178715011	chr2:179579740;179579739;179579738
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-72
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.3853
• 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	rs1342253967	None	0.381	D	0.559	0.291	0.524792858863	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	9.65E-05	1.30976E-04	0	0	0	None	0	0	0	0	4.77555E-04
T/I	rs1342253967	None	0.381	D	0.559	0.291	0.524792858863	gnomAD-4.0.0	1.54037E-05	None	None	None	None	N	None	6.7675E-05	3.39064E-05	None	0	0	None	0	0	0	0	1.70911E-04
T/S	None	None	0.001	N	0.195	0.123	0.281381271821	gnomAD-4.0.0	1.59528E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86664E-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
T/A	0.0717	likely_benign	0.0818	benign	-0.805	Destabilizing	None	N	0.249	neutral	D	0.522055904	None	None	N
T/C	0.2909	likely_benign	0.3649	ambiguous	-0.428	Destabilizing	0.99	D	0.607	neutral	None	None	None	None	N
T/D	0.2548	likely_benign	0.3648	ambiguous	-0.233	Destabilizing	0.551	D	0.581	neutral	None	None	None	None	N
T/E	0.2513	likely_benign	0.3578	ambiguous	-0.239	Destabilizing	0.538	D	0.551	neutral	None	None	None	None	N
T/F	0.1048	likely_benign	0.1337	benign	-0.833	Destabilizing	0.939	D	0.656	neutral	None	None	None	None	N
T/G	0.1814	likely_benign	0.2307	benign	-1.062	Destabilizing	0.594	D	0.555	neutral	None	None	None	None	N
T/H	0.1675	likely_benign	0.208	benign	-1.285	Destabilizing	0.978	D	0.657	neutral	None	None	None	None	N
T/I	0.0777	likely_benign	0.0921	benign	-0.212	Destabilizing	0.381	N	0.559	neutral	D	0.537102714	None	None	N
T/K	0.1838	likely_benign	0.268	benign	-0.813	Destabilizing	0.449	N	0.549	neutral	None	None	None	None	N
T/L	0.0703	likely_benign	0.0814	benign	-0.212	Destabilizing	0.005	N	0.374	neutral	None	None	None	None	N
T/M	0.0777	likely_benign	0.0869	benign	0.043	Stabilizing	0.851	D	0.627	neutral	None	None	None	None	N
T/N	0.0861	likely_benign	0.1008	benign	-0.669	Destabilizing	0.317	N	0.518	neutral	N	0.516746084	None	None	N
T/P	0.2566	likely_benign	0.3464	ambiguous	-0.377	Destabilizing	0.652	D	0.624	neutral	N	0.51012105	None	None	N
T/Q	0.2032	likely_benign	0.2594	benign	-0.824	Destabilizing	0.728	D	0.625	neutral	None	None	None	None	N
T/R	0.1395	likely_benign	0.2052	benign	-0.541	Destabilizing	0.939	D	0.623	neutral	None	None	None	None	N
T/S	0.0757	likely_benign	0.0877	benign	-0.933	Destabilizing	0.001	N	0.195	neutral	N	0.429895104	None	None	N
T/V	0.0797	likely_benign	0.0901	benign	-0.377	Destabilizing	0.368	N	0.513	neutral	None	None	None	None	N
T/W	0.388	ambiguous	0.4937	ambiguous	-0.778	Destabilizing	0.997	D	0.703	prob.neutral	None	None	None	None	N
T/Y	0.153	likely_benign	0.186	benign	-0.57	Destabilizing	0.99	D	0.659	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.