TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23353	70282;70283;70284	chr2:178576075;178576074;178576073	chr2:179440802;179440801;179440800
N2AB	21712	65359;65360;65361	chr2:178576075;178576074;178576073	chr2:179440802;179440801;179440800
N2A	20785	62578;62579;62580	chr2:178576075;178576074;178576073	chr2:179440802;179440801;179440800
N2B	14288	43087;43088;43089	chr2:178576075;178576074;178576073	chr2:179440802;179440801;179440800
Novex-1	14413	43462;43463;43464	chr2:178576075;178576074;178576073	chr2:179440802;179440801;179440800
Novex-2	14480	43663;43664;43665	chr2:178576075;178576074;178576073	chr2:179440802;179440801;179440800
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-129
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3749
• 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	rs1709976943	None	0.994	N	0.662	0.38	0.299427821978	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1709976943	None	0.994	N	0.662	0.38	0.299427821978	gnomAD-4.0.0	6.57678E-06	None	None	None	None	N	None	2.41383E-05	0	None	0	0	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	0.2582	likely_benign	0.2464	benign	-0.62	Destabilizing	0.958	D	0.393	neutral	N	0.47129257	None	None	N
T/C	0.6391	likely_pathogenic	0.6492	pathogenic	-0.423	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
T/D	0.8878	likely_pathogenic	0.8552	pathogenic	0.187	Stabilizing	0.938	D	0.539	neutral	None	None	None	None	N
T/E	0.8432	likely_pathogenic	0.797	pathogenic	0.159	Stabilizing	0.18	N	0.309	neutral	None	None	None	None	N
T/F	0.6514	likely_pathogenic	0.6564	pathogenic	-0.834	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	N
T/G	0.4689	ambiguous	0.4735	ambiguous	-0.832	Destabilizing	0.991	D	0.609	neutral	None	None	None	None	N
T/H	0.6512	likely_pathogenic	0.6389	pathogenic	-1.115	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
T/I	0.4456	ambiguous	0.3945	ambiguous	-0.163	Destabilizing	0.994	D	0.662	neutral	N	0.511773755	None	None	N
T/K	0.7747	likely_pathogenic	0.761	pathogenic	-0.573	Destabilizing	0.919	D	0.576	neutral	N	0.468521623	None	None	N
T/L	0.2722	likely_benign	0.2585	benign	-0.163	Destabilizing	0.968	D	0.53	neutral	None	None	None	None	N
T/M	0.1733	likely_benign	0.1681	benign	0.016	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
T/N	0.3091	likely_benign	0.2683	benign	-0.432	Destabilizing	0.991	D	0.594	neutral	None	None	None	None	N
T/P	0.4858	ambiguous	0.4513	ambiguous	-0.283	Destabilizing	0.994	D	0.661	neutral	N	0.484528439	None	None	N
T/Q	0.6201	likely_pathogenic	0.5759	pathogenic	-0.599	Destabilizing	0.982	D	0.661	neutral	None	None	None	None	N
T/R	0.7585	likely_pathogenic	0.7453	pathogenic	-0.358	Destabilizing	0.988	D	0.658	neutral	N	0.475332952	None	None	N
T/S	0.2837	likely_benign	0.2658	benign	-0.718	Destabilizing	0.958	D	0.381	neutral	N	0.479543906	None	None	N
T/V	0.2951	likely_benign	0.278	benign	-0.283	Destabilizing	0.984	D	0.445	neutral	None	None	None	None	N
T/W	0.9025	likely_pathogenic	0.9122	pathogenic	-0.781	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
T/Y	0.658	likely_pathogenic	0.6645	pathogenic	-0.536	Destabilizing	0.998	D	0.692	prob.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.