TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2413	7462;7463;7464	chr2:178773931;178773930;178773929	chr2:179638658;179638657;179638656
N2AB	2413	7462;7463;7464	chr2:178773931;178773930;178773929	chr2:179638658;179638657;179638656
N2A	2413	7462;7463;7464	chr2:178773931;178773930;178773929	chr2:179638658;179638657;179638656
N2B	2367	7324;7325;7326	chr2:178773931;178773930;178773929	chr2:179638658;179638657;179638656
Novex-1	2367	7324;7325;7326	chr2:178773931;178773930;178773929	chr2:179638658;179638657;179638656
Novex-2	2367	7324;7325;7326	chr2:178773931;178773930;178773929	chr2:179638658;179638657;179638656
Novex-3	2413	7462;7463;7464	chr2:178773931;178773930;178773929	chr2:179638658;179638657;179638656

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-13
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.2169
• 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
L/F	rs780754758	-1.723	1.0	D	0.671	0.292	0.734323642297	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/F	rs780754758	-1.723	1.0	D	0.671	0.292	0.734323642297	gnomAD-4.0.0	1.36815E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	1.65585E-05

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
L/A	0.934	likely_pathogenic	0.9234	pathogenic	-2.774	Highly Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
L/C	0.9441	likely_pathogenic	0.9372	pathogenic	-1.785	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/D	0.9965	likely_pathogenic	0.9958	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/E	0.9774	likely_pathogenic	0.9714	pathogenic	-3.001	Highly Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
L/F	0.7228	likely_pathogenic	0.6956	pathogenic	-1.716	Destabilizing	1.0	D	0.671	neutral	D	0.541720874	None	None	N
L/G	0.9871	likely_pathogenic	0.9857	pathogenic	-3.244	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/H	0.9221	likely_pathogenic	0.9101	pathogenic	-2.684	Highly Destabilizing	1.0	D	0.801	deleterious	N	0.511406596	None	None	N
L/I	0.321	likely_benign	0.2963	benign	-1.418	Destabilizing	0.999	D	0.477	neutral	N	0.488826372	None	None	N
L/K	0.9407	likely_pathogenic	0.9337	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/M	0.4053	ambiguous	0.3792	ambiguous	-1.097	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
L/N	0.9725	likely_pathogenic	0.9691	pathogenic	-2.495	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/P	0.9975	likely_pathogenic	0.9975	pathogenic	-1.853	Destabilizing	1.0	D	0.8	deleterious	D	0.609762579	None	None	N
L/Q	0.8919	likely_pathogenic	0.8706	pathogenic	-2.459	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/R	0.8868	likely_pathogenic	0.876	pathogenic	-1.841	Destabilizing	1.0	D	0.786	deleterious	N	0.504291236	None	None	N
L/S	0.9755	likely_pathogenic	0.9699	pathogenic	-3.09	Highly Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
L/T	0.9018	likely_pathogenic	0.8901	pathogenic	-2.811	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
L/V	0.3956	ambiguous	0.3595	ambiguous	-1.853	Destabilizing	0.999	D	0.503	neutral	N	0.470888154	None	None	N
L/W	0.9093	likely_pathogenic	0.8947	pathogenic	-2.143	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/Y	0.9293	likely_pathogenic	0.9216	pathogenic	-1.934	Destabilizing	1.0	D	0.773	deleterious	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.