TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17812	53659;53660;53661	chr2:178607168;178607167;178607166	chr2:179471895;179471894;179471893
N2AB	16171	48736;48737;48738	chr2:178607168;178607167;178607166	chr2:179471895;179471894;179471893
N2A	15244	45955;45956;45957	chr2:178607168;178607167;178607166	chr2:179471895;179471894;179471893
N2B	8747	26464;26465;26466	chr2:178607168;178607167;178607166	chr2:179471895;179471894;179471893
Novex-1	8872	26839;26840;26841	chr2:178607168;178607167;178607166	chr2:179471895;179471894;179471893
Novex-2	8939	27040;27041;27042	chr2:178607168;178607167;178607166	chr2:179471895;179471894;179471893
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-17
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.6999
• 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
R/S	None	None	1.0	N	0.653	0.307	0.338110398507	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
R/A	0.9718	likely_pathogenic	0.9631	pathogenic	0.045	Stabilizing	0.999	D	0.622	neutral	None	None	None	None	N
R/C	0.7969	likely_pathogenic	0.7497	pathogenic	0.028	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
R/D	0.9887	likely_pathogenic	0.9882	pathogenic	-0.009	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
R/E	0.9464	likely_pathogenic	0.9373	pathogenic	0.098	Stabilizing	0.999	D	0.668	neutral	None	None	None	None	N
R/F	0.9661	likely_pathogenic	0.9509	pathogenic	0.097	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
R/G	0.9424	likely_pathogenic	0.9249	pathogenic	-0.225	Destabilizing	1.0	D	0.605	neutral	N	0.467214501	None	None	N
R/H	0.6266	likely_pathogenic	0.5515	ambiguous	-0.81	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
R/I	0.8764	likely_pathogenic	0.8405	pathogenic	0.742	Stabilizing	1.0	D	0.718	prob.delet.	N	0.467089976	None	None	N
R/K	0.5329	ambiguous	0.4871	ambiguous	0.005	Stabilizing	0.997	D	0.545	neutral	N	0.475400028	None	None	N
R/L	0.8474	likely_pathogenic	0.8053	pathogenic	0.742	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
R/M	0.9261	likely_pathogenic	0.8942	pathogenic	0.169	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
R/N	0.975	likely_pathogenic	0.9707	pathogenic	0.294	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
R/P	0.9859	likely_pathogenic	0.9838	pathogenic	0.532	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
R/Q	0.6219	likely_pathogenic	0.5284	ambiguous	0.25	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
R/S	0.9787	likely_pathogenic	0.9714	pathogenic	-0.069	Destabilizing	1.0	D	0.653	neutral	N	0.433649406	None	None	N
R/T	0.9537	likely_pathogenic	0.9393	pathogenic	0.198	Stabilizing	1.0	D	0.649	neutral	N	0.421874975	None	None	N
R/V	0.9138	likely_pathogenic	0.8881	pathogenic	0.532	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/W	0.7858	likely_pathogenic	0.7136	pathogenic	0.131	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
R/Y	0.9146	likely_pathogenic	0.8906	pathogenic	0.501	Stabilizing	1.0	D	0.701	prob.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.