TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18067	54424;54425;54426	chr2:178604890;178604889;178604888	chr2:179469617;179469616;179469615
N2AB	16426	49501;49502;49503	chr2:178604890;178604889;178604888	chr2:179469617;179469616;179469615
N2A	15499	46720;46721;46722	chr2:178604890;178604889;178604888	chr2:179469617;179469616;179469615
N2B	9002	27229;27230;27231	chr2:178604890;178604889;178604888	chr2:179469617;179469616;179469615
Novex-1	9127	27604;27605;27606	chr2:178604890;178604889;178604888	chr2:179469617;179469616;179469615
Novex-2	9194	27805;27806;27807	chr2:178604890;178604889;178604888	chr2:179469617;179469616;179469615
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-19
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1493
• 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/C	rs745390353	-0.771	0.989	N	0.733	0.367	0.411265580357	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.64E-05	None	0	None	0	0	0
S/T	None	None	0.022	N	0.304	0.074	0.199424873507	gnomAD-4.0.0	3.19328E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	4.84496E-04	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
S/A	0.1278	likely_benign	0.142	benign	-0.488	Destabilizing	0.005	N	0.334	neutral	N	0.503762852	None	None	N
S/C	0.3186	likely_benign	0.3262	benign	-0.597	Destabilizing	0.989	D	0.733	prob.delet.	N	0.489210005	None	None	N
S/D	0.7394	likely_pathogenic	0.7722	pathogenic	-1.467	Destabilizing	0.915	D	0.559	neutral	None	None	None	None	N
S/E	0.8436	likely_pathogenic	0.8415	pathogenic	-1.417	Destabilizing	0.842	D	0.547	neutral	None	None	None	None	N
S/F	0.5404	ambiguous	0.5765	pathogenic	-0.577	Destabilizing	0.934	D	0.775	deleterious	N	0.488956515	None	None	N
S/G	0.1193	likely_benign	0.1288	benign	-0.778	Destabilizing	0.525	D	0.538	neutral	None	None	None	None	N
S/H	0.7306	likely_pathogenic	0.7532	pathogenic	-1.368	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
S/I	0.6615	likely_pathogenic	0.6384	pathogenic	0.188	Stabilizing	0.728	D	0.709	prob.delet.	None	None	None	None	N
S/K	0.9375	likely_pathogenic	0.9403	pathogenic	-0.857	Destabilizing	0.842	D	0.553	neutral	None	None	None	None	N
S/L	0.1429	likely_benign	0.1785	benign	0.188	Stabilizing	0.007	N	0.459	neutral	None	None	None	None	N
S/M	0.3674	ambiguous	0.3827	ambiguous	0.429	Stabilizing	0.949	D	0.728	prob.delet.	None	None	None	None	N
S/N	0.4304	ambiguous	0.4433	ambiguous	-1.153	Destabilizing	0.915	D	0.583	neutral	None	None	None	None	N
S/P	0.9246	likely_pathogenic	0.9386	pathogenic	-0.002	Destabilizing	0.966	D	0.717	prob.delet.	N	0.488196046	None	None	N
S/Q	0.7921	likely_pathogenic	0.7999	pathogenic	-1.246	Destabilizing	0.974	D	0.589	neutral	None	None	None	None	N
S/R	0.9353	likely_pathogenic	0.9374	pathogenic	-0.817	Destabilizing	0.974	D	0.717	prob.delet.	None	None	None	None	N
S/T	0.1647	likely_benign	0.1697	benign	-0.901	Destabilizing	0.022	N	0.304	neutral	N	0.481771427	None	None	N
S/V	0.5671	likely_pathogenic	0.5751	pathogenic	-0.002	Destabilizing	0.525	D	0.674	neutral	None	None	None	None	N
S/W	0.7826	likely_pathogenic	0.7963	pathogenic	-0.737	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
S/Y	0.5406	ambiguous	0.5715	pathogenic	-0.38	Destabilizing	0.989	D	0.794	deleterious	N	0.488956515	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.