TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30474	91645;91646;91647	chr2:178551111;178551110;178551109	chr2:179415838;179415837;179415836
N2AB	28833	86722;86723;86724	chr2:178551111;178551110;178551109	chr2:179415838;179415837;179415836
N2A	27906	83941;83942;83943	chr2:178551111;178551110;178551109	chr2:179415838;179415837;179415836
N2B	21409	64450;64451;64452	chr2:178551111;178551110;178551109	chr2:179415838;179415837;179415836
Novex-1	21534	64825;64826;64827	chr2:178551111;178551110;178551109	chr2:179415838;179415837;179415836
Novex-2	21601	65026;65027;65028	chr2:178551111;178551110;178551109	chr2:179415838;179415837;179415836
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: Fn3-110
• Domain position: 53
• Structural Position: 72
• Q(SASA): 0.735
• Predicted PPI site: I

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	rs1161044987	0.098	0.001	N	0.211	0.089	0.215109475489	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
T/I	rs1161044987	0.098	0.001	N	0.211	0.089	0.215109475489	gnomAD-4.0.0	1.59203E-06	None	None	None	None	I	None	5.65931E-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	0.0946	likely_benign	0.1257	benign	-0.314	Destabilizing	0.055	N	0.424	neutral	N	0.496354091	None	None	I
T/C	0.5234	ambiguous	0.5704	pathogenic	-0.325	Destabilizing	0.909	D	0.436	neutral	None	None	None	None	I
T/D	0.6693	likely_pathogenic	0.7488	pathogenic	0.203	Stabilizing	0.396	N	0.374	neutral	None	None	None	None	I
T/E	0.5793	likely_pathogenic	0.6834	pathogenic	0.127	Stabilizing	0.396	N	0.369	neutral	None	None	None	None	I
T/F	0.4494	ambiguous	0.5331	ambiguous	-0.882	Destabilizing	0.567	D	0.515	neutral	None	None	None	None	I
T/G	0.249	likely_benign	0.3252	benign	-0.42	Destabilizing	0.157	N	0.445	neutral	None	None	None	None	I
T/H	0.4043	ambiguous	0.4624	ambiguous	-0.61	Destabilizing	0.909	D	0.541	neutral	None	None	None	None	I
T/I	0.2615	likely_benign	0.3255	benign	-0.155	Destabilizing	0.001	N	0.211	neutral	N	0.493431216	None	None	I
T/K	0.4537	ambiguous	0.5501	ambiguous	-0.291	Destabilizing	0.396	N	0.372	neutral	None	None	None	None	I
T/L	0.1439	likely_benign	0.1783	benign	-0.155	Destabilizing	0.072	N	0.462	neutral	None	None	None	None	I
T/M	0.1185	likely_benign	0.1409	benign	-0.13	Destabilizing	0.567	D	0.413	neutral	None	None	None	None	I
T/N	0.1794	likely_benign	0.2204	benign	-0.114	Destabilizing	0.331	N	0.357	neutral	N	0.488428041	None	None	I
T/P	0.4516	ambiguous	0.5394	ambiguous	-0.181	Destabilizing	0.497	N	0.399	neutral	N	0.464653153	None	None	I
T/Q	0.3466	ambiguous	0.4057	ambiguous	-0.305	Destabilizing	0.567	D	0.375	neutral	None	None	None	None	I
T/R	0.3745	ambiguous	0.4561	ambiguous	-0.005	Destabilizing	0.567	D	0.393	neutral	None	None	None	None	I
T/S	0.1116	likely_benign	0.144	benign	-0.313	Destabilizing	0.001	N	0.219	neutral	N	0.44740535	None	None	I
T/V	0.1811	likely_benign	0.2214	benign	-0.181	Destabilizing	0.072	N	0.433	neutral	None	None	None	None	I
T/W	0.773	likely_pathogenic	0.8098	pathogenic	-0.925	Destabilizing	0.968	D	0.616	neutral	None	None	None	None	I
T/Y	0.4889	ambiguous	0.5474	ambiguous	-0.618	Destabilizing	0.726	D	0.52	neutral	None	None	None	None	I

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.