TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15282	46069;46070;46071	chr2:178620766;178620765;178620764	chr2:179485493;179485492;179485491
N2AB	13641	41146;41147;41148	chr2:178620766;178620765;178620764	chr2:179485493;179485492;179485491
N2A	12714	38365;38366;38367	chr2:178620766;178620765;178620764	chr2:179485493;179485492;179485491
N2B	6217	18874;18875;18876	chr2:178620766;178620765;178620764	chr2:179485493;179485492;179485491
Novex-1	6342	19249;19250;19251	chr2:178620766;178620765;178620764	chr2:179485493;179485492;179485491
Novex-2	6409	19450;19451;19452	chr2:178620766;178620765;178620764	chr2:179485493;179485492;179485491
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-104
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.2788
• 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/A	rs1248616113	None	0.046	D	0.285	0.194	0.314417295294	gnomAD-4.0.0	4.79218E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29941E-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	0.1145	likely_benign	0.1178	benign	-0.859	Destabilizing	0.046	N	0.285	neutral	D	0.556422187	None	None	N
T/C	0.5303	ambiguous	0.5142	ambiguous	-0.642	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
T/D	0.6707	likely_pathogenic	0.6887	pathogenic	-0.647	Destabilizing	0.986	D	0.622	neutral	None	None	None	None	N
T/E	0.4838	ambiguous	0.4997	ambiguous	-0.65	Destabilizing	0.986	D	0.63	neutral	None	None	None	None	N
T/F	0.3524	ambiguous	0.3427	ambiguous	-1.186	Destabilizing	0.993	D	0.767	deleterious	None	None	None	None	N
T/G	0.3919	ambiguous	0.3846	ambiguous	-1.08	Destabilizing	0.91	D	0.672	neutral	None	None	None	None	N
T/H	0.3593	ambiguous	0.3688	ambiguous	-1.49	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
T/I	0.2178	likely_benign	0.212	benign	-0.361	Destabilizing	0.982	D	0.672	neutral	D	0.547050884	None	None	N
T/K	0.3378	likely_benign	0.3512	ambiguous	-0.613	Destabilizing	0.986	D	0.634	neutral	None	None	None	None	N
T/L	0.1606	likely_benign	0.1516	benign	-0.361	Destabilizing	0.953	D	0.596	neutral	None	None	None	None	N
T/M	0.1234	likely_benign	0.118	benign	0.092	Stabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
T/N	0.205	likely_benign	0.2063	benign	-0.655	Destabilizing	0.982	D	0.641	neutral	D	0.576009236	None	None	N
T/P	0.5679	likely_pathogenic	0.6344	pathogenic	-0.498	Destabilizing	0.991	D	0.678	prob.neutral	D	0.642422197	None	None	N
T/Q	0.276	likely_benign	0.279	benign	-0.928	Destabilizing	0.993	D	0.691	prob.neutral	None	None	None	None	N
T/R	0.254	likely_benign	0.2646	benign	-0.375	Destabilizing	0.986	D	0.689	prob.neutral	None	None	None	None	N
T/S	0.1389	likely_benign	0.1358	benign	-0.899	Destabilizing	0.17	N	0.36	neutral	N	0.503765598	None	None	N
T/V	0.1803	likely_benign	0.1731	benign	-0.498	Destabilizing	0.91	D	0.587	neutral	None	None	None	None	N
T/W	0.7031	likely_pathogenic	0.6968	pathogenic	-1.113	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
T/Y	0.4188	ambiguous	0.4177	ambiguous	-0.825	Destabilizing	0.998	D	0.763	deleterious	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.