TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14123	42592;42593;42594	chr2:178634414;178634413;178634412	chr2:179499141;179499140;179499139
N2AB	12482	37669;37670;37671	chr2:178634414;178634413;178634412	chr2:179499141;179499140;179499139
N2A	11555	34888;34889;34890	chr2:178634414;178634413;178634412	chr2:179499141;179499140;179499139
N2B	5058	15397;15398;15399	chr2:178634414;178634413;178634412	chr2:179499141;179499140;179499139
Novex-1	5183	15772;15773;15774	chr2:178634414;178634413;178634412	chr2:179499141;179499140;179499139
Novex-2	5250	15973;15974;15975	chr2:178634414;178634413;178634412	chr2:179499141;179499140;179499139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-91
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.2803
• 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
T/S	None	None	0.374	N	0.454	0.135	0.12205267543	gnomAD-4.0.0	1.5931E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86077E-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
T/A	0.1271	likely_benign	0.1424	benign	-1.398	Destabilizing	0.76	D	0.551	neutral	N	0.444685224	None	None	N
T/C	0.4695	ambiguous	0.505	ambiguous	-1.019	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
T/D	0.6061	likely_pathogenic	0.6314	pathogenic	-1.127	Destabilizing	0.986	D	0.642	neutral	None	None	None	None	N
T/E	0.3816	ambiguous	0.4342	ambiguous	-0.944	Destabilizing	0.986	D	0.64	neutral	None	None	None	None	N
T/F	0.2847	likely_benign	0.3454	ambiguous	-1.257	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
T/G	0.4336	ambiguous	0.4953	ambiguous	-1.784	Destabilizing	0.06	N	0.479	neutral	None	None	None	None	N
T/H	0.2957	likely_benign	0.3578	ambiguous	-1.819	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
T/I	0.2133	likely_benign	0.2389	benign	-0.387	Destabilizing	0.991	D	0.678	prob.neutral	N	0.502928138	None	None	N
T/K	0.3342	likely_benign	0.3877	ambiguous	-0.371	Destabilizing	0.986	D	0.636	neutral	None	None	None	None	N
T/L	0.1482	likely_benign	0.1803	benign	-0.387	Destabilizing	0.976	D	0.587	neutral	None	None	None	None	N
T/M	0.1052	likely_benign	0.1215	benign	-0.311	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	N
T/N	0.2226	likely_benign	0.229	benign	-0.978	Destabilizing	0.982	D	0.51	neutral	D	0.634946974	None	None	N
T/P	0.9073	likely_pathogenic	0.9173	pathogenic	-0.695	Destabilizing	0.991	D	0.677	prob.neutral	D	0.635083753	None	None	N
T/Q	0.2849	likely_benign	0.3454	ambiguous	-0.856	Destabilizing	0.993	D	0.675	prob.neutral	None	None	None	None	N
T/R	0.244	likely_benign	0.2943	benign	-0.513	Destabilizing	0.993	D	0.674	neutral	None	None	None	None	N
T/S	0.1311	likely_benign	0.1439	benign	-1.34	Destabilizing	0.374	N	0.454	neutral	N	0.446378236	None	None	N
T/V	0.1658	likely_benign	0.1924	benign	-0.695	Destabilizing	0.976	D	0.509	neutral	None	None	None	None	N
T/W	0.6598	likely_pathogenic	0.7591	pathogenic	-1.242	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
T/Y	0.344	ambiguous	0.4203	ambiguous	-0.903	Destabilizing	0.998	D	0.757	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.