TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8282	25069;25070;25071	chr2:178718162;178718161;178718160	chr2:179582889;179582888;179582887
N2AB	7965	24118;24119;24120	chr2:178718162;178718161;178718160	chr2:179582889;179582888;179582887
N2A	7038	21337;21338;21339	chr2:178718162;178718161;178718160	chr2:179582889;179582888;179582887
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-68
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.6361
• 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/A	rs2077783131	None	0.002	D	0.302	0.234	0.202949470691	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
T/I	None	None	0.685	N	0.507	0.232	0.452264262256	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0839	likely_benign	0.0892	benign	-0.539	Destabilizing	0.002	N	0.302	neutral	D	0.535566705	None	None	I
T/C	0.4329	ambiguous	0.4208	ambiguous	-0.445	Destabilizing	0.997	D	0.557	neutral	None	None	None	None	I
T/D	0.4564	ambiguous	0.471	ambiguous	0.258	Stabilizing	0.382	N	0.499	neutral	None	None	None	None	I
T/E	0.2874	likely_benign	0.3016	benign	0.256	Stabilizing	0.804	D	0.512	neutral	None	None	None	None	I
T/F	0.1577	likely_benign	0.1474	benign	-0.711	Destabilizing	0.964	D	0.604	neutral	None	None	None	None	I
T/G	0.329	likely_benign	0.3418	ambiguous	-0.774	Destabilizing	0.681	D	0.516	neutral	None	None	None	None	I
T/H	0.2047	likely_benign	0.2113	benign	-0.966	Destabilizing	0.976	D	0.578	neutral	None	None	None	None	I
T/I	0.0992	likely_benign	0.0874	benign	-0.016	Destabilizing	0.685	D	0.507	neutral	N	0.517095588	None	None	I
T/K	0.1738	likely_benign	0.1969	benign	-0.457	Destabilizing	0.852	D	0.511	neutral	None	None	None	None	I
T/L	0.0762	likely_benign	0.0773	benign	-0.016	Destabilizing	0.543	D	0.475	neutral	None	None	None	None	I
T/M	0.0832	likely_benign	0.0798	benign	-0.014	Destabilizing	0.976	D	0.565	neutral	None	None	None	None	I
T/N	0.1362	likely_benign	0.1341	benign	-0.434	Destabilizing	0.012	N	0.427	neutral	D	0.541300599	None	None	I
T/P	0.2838	likely_benign	0.3601	ambiguous	-0.157	Destabilizing	0.869	D	0.589	neutral	D	0.534940936	None	None	I
T/Q	0.1962	likely_benign	0.2145	benign	-0.521	Destabilizing	0.95	D	0.597	neutral	None	None	None	None	I
T/R	0.1314	likely_benign	0.1527	benign	-0.272	Destabilizing	0.982	D	0.588	neutral	None	None	None	None	I
T/S	0.1111	likely_benign	0.1102	benign	-0.72	Destabilizing	0.004	N	0.349	neutral	N	0.471304583	None	None	I
T/V	0.0892	likely_benign	0.078	benign	-0.157	Destabilizing	0.005	N	0.322	neutral	None	None	None	None	I
T/W	0.5159	ambiguous	0.5346	ambiguous	-0.701	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	I
T/Y	0.1971	likely_benign	0.1962	benign	-0.421	Destabilizing	0.171	N	0.528	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.