TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2742	8449;8450;8451	chr2:178770568;178770567;178770566	chr2:179635295;179635294;179635293
N2AB	2742	8449;8450;8451	chr2:178770568;178770567;178770566	chr2:179635295;179635294;179635293
N2A	2742	8449;8450;8451	chr2:178770568;178770567;178770566	chr2:179635295;179635294;179635293
N2B	2696	8311;8312;8313	chr2:178770568;178770567;178770566	chr2:179635295;179635294;179635293
Novex-1	2696	8311;8312;8313	chr2:178770568;178770567;178770566	chr2:179635295;179635294;179635293
Novex-2	2696	8311;8312;8313	chr2:178770568;178770567;178770566	chr2:179635295;179635294;179635293
Novex-3	2742	8449;8450;8451	chr2:178770568;178770567;178770566	chr2:179635295;179635294;179635293

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-17
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1295
• 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
K/Q	rs1357613078	-0.771	0.83	D	0.689	0.772	0.524063890018	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
K/Q	rs1357613078	-0.771	0.83	D	0.689	0.772	0.524063890018	gnomAD-4.0.0	1.59049E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85649E-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
K/A	0.8427	likely_pathogenic	0.9349	pathogenic	-1.299	Destabilizing	0.648	D	0.561	neutral	None	None	None	None	N
K/C	0.7908	likely_pathogenic	0.8903	pathogenic	-1.248	Destabilizing	0.993	D	0.848	deleterious	None	None	None	None	N
K/D	0.9719	likely_pathogenic	0.9916	pathogenic	-0.564	Destabilizing	0.866	D	0.781	deleterious	None	None	None	None	N
K/E	0.6381	likely_pathogenic	0.8056	pathogenic	-0.341	Destabilizing	0.41	N	0.491	neutral	D	0.70959231	None	None	N
K/F	0.9573	likely_pathogenic	0.9832	pathogenic	-0.868	Destabilizing	0.98	D	0.833	deleterious	None	None	None	None	N
K/G	0.8945	likely_pathogenic	0.9687	pathogenic	-1.738	Destabilizing	0.866	D	0.729	prob.delet.	None	None	None	None	N
K/H	0.5411	ambiguous	0.6611	pathogenic	-1.837	Destabilizing	0.98	D	0.784	deleterious	None	None	None	None	N
K/I	0.7346	likely_pathogenic	0.8672	pathogenic	-0.094	Destabilizing	0.908	D	0.847	deleterious	D	0.710712807	None	None	N
K/L	0.7259	likely_pathogenic	0.8468	pathogenic	-0.094	Destabilizing	0.866	D	0.729	prob.delet.	None	None	None	None	N
K/M	0.6228	likely_pathogenic	0.7372	pathogenic	-0.244	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
K/N	0.8993	likely_pathogenic	0.9577	pathogenic	-1.092	Destabilizing	0.83	D	0.703	prob.neutral	D	0.70959231	None	None	N
K/P	0.9882	likely_pathogenic	0.9973	pathogenic	-0.47	Destabilizing	0.929	D	0.783	deleterious	None	None	None	None	N
K/Q	0.2737	likely_benign	0.3629	ambiguous	-0.954	Destabilizing	0.83	D	0.689	prob.neutral	D	0.710976074	None	None	N
K/R	0.0753	likely_benign	0.0888	benign	-0.693	Destabilizing	0.01	N	0.333	neutral	D	0.545715304	None	None	N
K/S	0.8876	likely_pathogenic	0.9549	pathogenic	-1.888	Destabilizing	0.648	D	0.548	neutral	None	None	None	None	N
K/T	0.7619	likely_pathogenic	0.901	pathogenic	-1.403	Destabilizing	0.83	D	0.733	prob.delet.	D	0.70981102	None	None	N
K/V	0.734	likely_pathogenic	0.8641	pathogenic	-0.47	Destabilizing	0.866	D	0.794	deleterious	None	None	None	None	N
K/W	0.8981	likely_pathogenic	0.9556	pathogenic	-0.697	Destabilizing	0.993	D	0.831	deleterious	None	None	None	None	N
K/Y	0.8767	likely_pathogenic	0.9351	pathogenic	-0.4	Destabilizing	0.929	D	0.83	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.