TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8942	27049;27050;27051	chr2:178713310;178713309;178713308	chr2:179578037;179578036;179578035
N2AB	8625	26098;26099;26100	chr2:178713310;178713309;178713308	chr2:179578037;179578036;179578035
N2A	7698	23317;23318;23319	chr2:178713310;178713309;178713308	chr2:179578037;179578036;179578035
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-75
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3967
• 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
S/L	None	None	0.006	N	0.285	0.265	0.430579932962	gnomAD-4.0.0	6.95618E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.10152E-07	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
S/A	0.0807	likely_benign	0.0877	benign	-0.578	Destabilizing	0.01	N	0.118	neutral	N	0.446532985	None	None	N
S/C	0.1695	likely_benign	0.1859	benign	-0.376	Destabilizing	0.017	N	0.271	neutral	None	None	None	None	N
S/D	0.4859	ambiguous	0.5008	ambiguous	0.022	Stabilizing	0.704	D	0.237	neutral	None	None	None	None	N
S/E	0.6379	likely_pathogenic	0.6249	pathogenic	-0.048	Destabilizing	0.704	D	0.236	neutral	None	None	None	None	N
S/F	0.2348	likely_benign	0.2412	benign	-1.057	Destabilizing	0.893	D	0.447	neutral	None	None	None	None	N
S/G	0.1328	likely_benign	0.136	benign	-0.732	Destabilizing	0.495	N	0.265	neutral	None	None	None	None	N
S/H	0.428	ambiguous	0.4067	ambiguous	-1.247	Destabilizing	0.981	D	0.403	neutral	None	None	None	None	N
S/I	0.2647	likely_benign	0.2791	benign	-0.296	Destabilizing	0.543	D	0.397	neutral	None	None	None	None	N
S/K	0.7538	likely_pathogenic	0.7408	pathogenic	-0.562	Destabilizing	0.031	N	0.15	neutral	None	None	None	None	N
S/L	0.1212	likely_benign	0.1349	benign	-0.296	Destabilizing	0.006	N	0.285	neutral	N	0.493748142	None	None	N
S/M	0.2517	likely_benign	0.2568	benign	0.074	Stabilizing	0.893	D	0.412	neutral	None	None	None	None	N
S/N	0.1921	likely_benign	0.2032	benign	-0.363	Destabilizing	0.704	D	0.312	neutral	None	None	None	None	N
S/P	0.1849	likely_benign	0.1944	benign	-0.36	Destabilizing	0.927	D	0.446	neutral	N	0.410476184	None	None	N
S/Q	0.5906	likely_pathogenic	0.5793	pathogenic	-0.631	Destabilizing	0.893	D	0.376	neutral	None	None	None	None	N
S/R	0.6514	likely_pathogenic	0.6333	pathogenic	-0.349	Destabilizing	0.543	D	0.423	neutral	None	None	None	None	N
S/T	0.0947	likely_benign	0.0957	benign	-0.474	Destabilizing	0.023	N	0.118	neutral	N	0.428483155	None	None	N
S/V	0.2178	likely_benign	0.2323	benign	-0.36	Destabilizing	0.329	N	0.393	neutral	None	None	None	None	N
S/W	0.4035	ambiguous	0.3958	ambiguous	-1.007	Destabilizing	0.995	D	0.477	neutral	None	None	None	None	N
S/Y	0.2307	likely_benign	0.232	benign	-0.75	Destabilizing	0.981	D	0.45	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.