TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18764	56515;56516;56517	chr2:178599611;178599610;178599609	chr2:179464338;179464337;179464336
N2AB	17123	51592;51593;51594	chr2:178599611;178599610;178599609	chr2:179464338;179464337;179464336
N2A	16196	48811;48812;48813	chr2:178599611;178599610;178599609	chr2:179464338;179464337;179464336
N2B	9699	29320;29321;29322	chr2:178599611;178599610;178599609	chr2:179464338;179464337;179464336
Novex-1	9824	29695;29696;29697	chr2:178599611;178599610;178599609	chr2:179464338;179464337;179464336
Novex-2	9891	29896;29897;29898	chr2:178599611;178599610;178599609	chr2:179464338;179464337;179464336
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-116
• Domain position: 77
• Structural Position: 156
• Q(SASA): 0.1046
• 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
I/N	None	None	0.912	N	0.83	0.475	0.751848519796	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	None	None	0.041	N	0.43	0.075	0.243398259712	gnomAD-4.0.0	1.60411E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88893E-05	0	0	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
I/A	0.9048	likely_pathogenic	0.8797	pathogenic	-2.579	Highly Destabilizing	0.207	N	0.693	prob.neutral	None	None	None	None	N
I/C	0.9462	likely_pathogenic	0.9299	pathogenic	-1.772	Destabilizing	0.981	D	0.765	deleterious	None	None	None	None	N
I/D	0.9991	likely_pathogenic	0.9981	pathogenic	-3.064	Highly Destabilizing	0.932	D	0.829	deleterious	None	None	None	None	N
I/E	0.9963	likely_pathogenic	0.9934	pathogenic	-2.797	Highly Destabilizing	0.818	D	0.816	deleterious	None	None	None	None	N
I/F	0.6635	likely_pathogenic	0.57	pathogenic	-1.53	Destabilizing	0.457	N	0.737	prob.delet.	N	0.507272012	None	None	N
I/G	0.992	likely_pathogenic	0.9872	pathogenic	-3.164	Highly Destabilizing	0.818	D	0.813	deleterious	None	None	None	None	N
I/H	0.996	likely_pathogenic	0.9915	pathogenic	-2.732	Highly Destabilizing	0.981	D	0.835	deleterious	None	None	None	None	N
I/K	0.9926	likely_pathogenic	0.9867	pathogenic	-1.923	Destabilizing	0.818	D	0.807	deleterious	None	None	None	None	N
I/L	0.097	likely_benign	0.0926	benign	-0.864	Destabilizing	None	N	0.348	neutral	N	0.389175405	None	None	N
I/M	0.2053	likely_benign	0.1835	benign	-0.824	Destabilizing	0.627	D	0.699	prob.neutral	N	0.489379685	None	None	N
I/N	0.9885	likely_pathogenic	0.977	pathogenic	-2.394	Highly Destabilizing	0.912	D	0.83	deleterious	N	0.508312162	None	None	N
I/P	0.9963	likely_pathogenic	0.9937	pathogenic	-1.42	Destabilizing	0.932	D	0.829	deleterious	None	None	None	None	N
I/Q	0.9924	likely_pathogenic	0.9859	pathogenic	-2.179	Highly Destabilizing	0.932	D	0.833	deleterious	None	None	None	None	N
I/R	0.9901	likely_pathogenic	0.9818	pathogenic	-1.767	Destabilizing	0.818	D	0.828	deleterious	None	None	None	None	N
I/S	0.9828	likely_pathogenic	0.9678	pathogenic	-3.064	Highly Destabilizing	0.773	D	0.769	deleterious	N	0.508138804	None	None	N
I/T	0.9586	likely_pathogenic	0.9376	pathogenic	-2.644	Highly Destabilizing	0.324	N	0.7	prob.neutral	N	0.507965446	None	None	N
I/V	0.0963	likely_benign	0.0946	benign	-1.42	Destabilizing	0.041	N	0.43	neutral	N	0.381286641	None	None	N
I/W	0.9939	likely_pathogenic	0.9882	pathogenic	-1.998	Destabilizing	0.981	D	0.831	deleterious	None	None	None	None	N
I/Y	0.9781	likely_pathogenic	0.9578	pathogenic	-1.692	Destabilizing	0.818	D	0.76	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.