TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21340	64243;64244;64245	chr2:178587193;178587192;178587191	chr2:179451920;179451919;179451918
N2AB	19699	59320;59321;59322	chr2:178587193;178587192;178587191	chr2:179451920;179451919;179451918
N2A	18772	56539;56540;56541	chr2:178587193;178587192;178587191	chr2:179451920;179451919;179451918
N2B	12275	37048;37049;37050	chr2:178587193;178587192;178587191	chr2:179451920;179451919;179451918
Novex-1	12400	37423;37424;37425	chr2:178587193;178587192;178587191	chr2:179451920;179451919;179451918
Novex-2	12467	37624;37625;37626	chr2:178587193;178587192;178587191	chr2:179451920;179451919;179451918
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-42
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0829
• 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
V/A	rs2049206770	None	0.999	D	0.64	0.758	0.828767969993	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86048E-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
V/A	0.8679	likely_pathogenic	0.8708	pathogenic	-2.412	Highly Destabilizing	0.999	D	0.64	neutral	D	0.550175263	None	None	N
V/C	0.957	likely_pathogenic	0.9613	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/D	0.9993	likely_pathogenic	0.9992	pathogenic	-3.432	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/E	0.9975	likely_pathogenic	0.997	pathogenic	-3.132	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.630412324	None	None	N
V/F	0.9224	likely_pathogenic	0.9186	pathogenic	-1.256	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/G	0.9467	likely_pathogenic	0.9438	pathogenic	-2.989	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.630412324	None	None	N
V/H	0.9991	likely_pathogenic	0.999	pathogenic	-2.847	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/I	0.1021	likely_benign	0.11	benign	-0.73	Destabilizing	0.997	D	0.603	neutral	N	0.496488242	None	None	N
V/K	0.9979	likely_pathogenic	0.9974	pathogenic	-1.945	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/L	0.7402	likely_pathogenic	0.751	pathogenic	-0.73	Destabilizing	0.997	D	0.649	neutral	N	0.514025524	None	None	N
V/M	0.7824	likely_pathogenic	0.7923	pathogenic	-1.098	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/N	0.9961	likely_pathogenic	0.9958	pathogenic	-2.572	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
V/P	0.9975	likely_pathogenic	0.9972	pathogenic	-1.273	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/Q	0.9966	likely_pathogenic	0.9958	pathogenic	-2.243	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/R	0.9962	likely_pathogenic	0.9949	pathogenic	-1.976	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
V/S	0.9773	likely_pathogenic	0.9774	pathogenic	-3.07	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/T	0.9335	likely_pathogenic	0.9365	pathogenic	-2.625	Highly Destabilizing	0.999	D	0.66	neutral	None	None	None	None	N
V/W	0.9993	likely_pathogenic	0.9993	pathogenic	-1.868	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/Y	0.9952	likely_pathogenic	0.9949	pathogenic	-1.581	Destabilizing	1.0	D	0.816	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.