TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33729	101410;101411;101412	chr2:178535430;178535429;178535428	chr2:179400157;179400156;179400155
N2AB	32088	96487;96488;96489	chr2:178535430;178535429;178535428	chr2:179400157;179400156;179400155
N2A	31161	93706;93707;93708	chr2:178535430;178535429;178535428	chr2:179400157;179400156;179400155
N2B	24664	74215;74216;74217	chr2:178535430;178535429;178535428	chr2:179400157;179400156;179400155
Novex-1	24789	74590;74591;74592	chr2:178535430;178535429;178535428	chr2:179400157;179400156;179400155
Novex-2	24856	74791;74792;74793	chr2:178535430;178535429;178535428	chr2:179400157;179400156;179400155
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-132
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.075
• 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
C/Y	None	None	0.999	N	0.707	0.403	0.704489790954	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85794E-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
C/A	0.6825	likely_pathogenic	0.5882	pathogenic	-1.378	Destabilizing	0.846	D	0.557	neutral	None	None	None	None	N
C/D	0.9828	likely_pathogenic	0.9617	pathogenic	-1.064	Destabilizing	0.977	D	0.773	deleterious	None	None	None	None	N
C/E	0.9576	likely_pathogenic	0.9091	pathogenic	-0.828	Destabilizing	0.984	D	0.756	deleterious	None	None	None	None	N
C/F	0.7021	likely_pathogenic	0.5106	ambiguous	-0.849	Destabilizing	0.999	D	0.707	prob.neutral	N	0.465204464	None	None	N
C/G	0.6074	likely_pathogenic	0.4675	ambiguous	-1.731	Destabilizing	0.981	D	0.733	prob.delet.	N	0.486888919	None	None	N
C/H	0.761	likely_pathogenic	0.6252	pathogenic	-2.035	Highly Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
C/I	0.8816	likely_pathogenic	0.7872	pathogenic	-0.425	Destabilizing	0.997	D	0.658	neutral	None	None	None	None	N
C/K	0.7869	likely_pathogenic	0.6602	pathogenic	-0.61	Destabilizing	0.96	D	0.717	prob.delet.	None	None	None	None	N
C/L	0.7839	likely_pathogenic	0.6517	pathogenic	-0.425	Destabilizing	0.98	D	0.601	neutral	None	None	None	None	N
C/M	0.8286	likely_pathogenic	0.7478	pathogenic	0.223	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
C/N	0.8425	likely_pathogenic	0.7662	pathogenic	-1.185	Destabilizing	0.978	D	0.771	deleterious	None	None	None	None	N
C/P	0.999	likely_pathogenic	0.9981	pathogenic	-0.72	Destabilizing	0.992	D	0.771	deleterious	None	None	None	None	N
C/Q	0.6275	likely_pathogenic	0.4983	ambiguous	-0.69	Destabilizing	0.984	D	0.773	deleterious	None	None	None	None	N
C/R	0.3893	ambiguous	0.2576	benign	-1.185	Destabilizing	0.207	N	0.584	neutral	N	0.378756129	None	None	N
C/S	0.6616	likely_pathogenic	0.555	ambiguous	-1.46	Destabilizing	0.91	D	0.648	neutral	N	0.461334653	None	None	N
C/T	0.8461	likely_pathogenic	0.7502	pathogenic	-1.036	Destabilizing	0.963	D	0.643	neutral	None	None	None	None	N
C/V	0.7741	likely_pathogenic	0.661	pathogenic	-0.72	Destabilizing	0.973	D	0.638	neutral	None	None	None	None	N
C/W	0.9166	likely_pathogenic	0.8033	pathogenic	-1.26	Destabilizing	1.0	D	0.709	prob.delet.	N	0.49315907	None	None	N
C/Y	0.709	likely_pathogenic	0.513	ambiguous	-1.008	Destabilizing	0.999	D	0.707	prob.neutral	N	0.491524274	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.