TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31570	94933;94934;94935	chr2:178546720;178546719;178546718	chr2:179411447;179411446;179411445
N2AB	29929	90010;90011;90012	chr2:178546720;178546719;178546718	chr2:179411447;179411446;179411445
N2A	29002	87229;87230;87231	chr2:178546720;178546719;178546718	chr2:179411447;179411446;179411445
N2B	22505	67738;67739;67740	chr2:178546720;178546719;178546718	chr2:179411447;179411446;179411445
Novex-1	22630	68113;68114;68115	chr2:178546720;178546719;178546718	chr2:179411447;179411446;179411445
Novex-2	22697	68314;68315;68316	chr2:178546720;178546719;178546718	chr2:179411447;179411446;179411445
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: Fn3-118
• Domain position: 65
• Structural Position: 92
• Q(SASA): 0.2329
• 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	rs1697325593	None	0.999	N	0.609	0.484	0.349429436713	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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	0.211	likely_benign	0.1708	benign	-0.856	Destabilizing	0.999	D	0.609	neutral	N	0.493683911	None	None	N
T/C	0.6726	likely_pathogenic	0.6212	pathogenic	-0.43	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/D	0.8157	likely_pathogenic	0.7449	pathogenic	0.641	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
T/E	0.6571	likely_pathogenic	0.5793	pathogenic	0.675	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
T/F	0.7377	likely_pathogenic	0.6606	pathogenic	-0.96	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
T/G	0.7367	likely_pathogenic	0.6582	pathogenic	-1.115	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
T/H	0.6014	likely_pathogenic	0.5158	ambiguous	-1.209	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
T/I	0.373	ambiguous	0.3356	benign	-0.252	Destabilizing	1.0	D	0.786	deleterious	N	0.5038749	None	None	N
T/K	0.5608	ambiguous	0.4816	ambiguous	-0.212	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
T/L	0.2475	likely_benign	0.2031	benign	-0.252	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
T/M	0.1629	likely_benign	0.1442	benign	-0.186	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/N	0.3816	ambiguous	0.3029	benign	-0.257	Destabilizing	1.0	D	0.705	prob.neutral	D	0.523026191	None	None	N
T/P	0.5053	ambiguous	0.3847	ambiguous	-0.422	Destabilizing	1.0	D	0.793	deleterious	N	0.490418681	None	None	N
T/Q	0.4616	ambiguous	0.3893	ambiguous	-0.3	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
T/R	0.5049	ambiguous	0.4265	ambiguous	-0.127	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/S	0.2701	likely_benign	0.2156	benign	-0.688	Destabilizing	0.999	D	0.568	neutral	N	0.490543585	None	None	N
T/V	0.2242	likely_benign	0.2071	benign	-0.422	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
T/W	0.9296	likely_pathogenic	0.9082	pathogenic	-0.877	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
T/Y	0.7723	likely_pathogenic	0.7018	pathogenic	-0.608	Destabilizing	1.0	D	0.859	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.