TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27458	82597;82598;82599	chr2:178563760;178563759;178563758	chr2:179428487;179428486;179428485
N2AB	25817	77674;77675;77676	chr2:178563760;178563759;178563758	chr2:179428487;179428486;179428485
N2A	24890	74893;74894;74895	chr2:178563760;178563759;178563758	chr2:179428487;179428486;179428485
N2B	18393	55402;55403;55404	chr2:178563760;178563759;178563758	chr2:179428487;179428486;179428485
Novex-1	18518	55777;55778;55779	chr2:178563760;178563759;178563758	chr2:179428487;179428486;179428485
Novex-2	18585	55978;55979;55980	chr2:178563760;178563759;178563758	chr2:179428487;179428486;179428485
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-87
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.3187
• 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/F	rs1335006996	-0.538	0.999	D	0.866	0.43	0.572964795716	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
S/F	rs1335006996	-0.538	0.999	D	0.866	0.43	0.572964795716	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
S/A	0.2728	likely_benign	0.2476	benign	-0.495	Destabilizing	0.994	D	0.539	neutral	N	0.489883751	None	None	N
S/C	0.3495	ambiguous	0.3181	benign	-0.257	Destabilizing	1.0	D	0.837	deleterious	N	0.508054139	None	None	N
S/D	0.945	likely_pathogenic	0.9357	pathogenic	-0.128	Destabilizing	0.998	D	0.792	deleterious	None	None	None	None	N
S/E	0.976	likely_pathogenic	0.9743	pathogenic	-0.017	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
S/F	0.9415	likely_pathogenic	0.9265	pathogenic	-0.42	Destabilizing	0.999	D	0.866	deleterious	D	0.538969504	None	None	N
S/G	0.3291	likely_benign	0.2744	benign	-0.843	Destabilizing	0.998	D	0.661	prob.neutral	None	None	None	None	N
S/H	0.9648	likely_pathogenic	0.957	pathogenic	-1.198	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
S/I	0.8435	likely_pathogenic	0.8196	pathogenic	0.351	Stabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
S/K	0.9955	likely_pathogenic	0.9948	pathogenic	-0.163	Destabilizing	0.998	D	0.778	deleterious	None	None	None	None	N
S/L	0.6271	likely_pathogenic	0.5805	pathogenic	0.351	Stabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
S/M	0.6988	likely_pathogenic	0.661	pathogenic	0.223	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
S/N	0.8451	likely_pathogenic	0.8202	pathogenic	-0.468	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
S/P	0.9789	likely_pathogenic	0.9775	pathogenic	0.106	Stabilizing	0.999	D	0.901	deleterious	N	0.480360643	None	None	N
S/Q	0.9767	likely_pathogenic	0.9742	pathogenic	-0.346	Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
S/R	0.9937	likely_pathogenic	0.9927	pathogenic	-0.404	Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
S/T	0.14	likely_benign	0.1311	benign	-0.339	Destabilizing	0.997	D	0.697	prob.delet.	N	0.46742463	None	None	N
S/V	0.7603	likely_pathogenic	0.7343	pathogenic	0.106	Stabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
S/W	0.9601	likely_pathogenic	0.9512	pathogenic	-0.556	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
S/Y	0.9221	likely_pathogenic	0.8995	pathogenic	-0.152	Destabilizing	0.999	D	0.875	deleterious	D	0.539222993	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.