TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32196	96811;96812;96813	chr2:178543387;178543386;178543385	chr2:179408114;179408113;179408112
N2AB	30555	91888;91889;91890	chr2:178543387;178543386;178543385	chr2:179408114;179408113;179408112
N2A	29628	89107;89108;89109	chr2:178543387;178543386;178543385	chr2:179408114;179408113;179408112
N2B	23131	69616;69617;69618	chr2:178543387;178543386;178543385	chr2:179408114;179408113;179408112
Novex-1	23256	69991;69992;69993	chr2:178543387;178543386;178543385	chr2:179408114;179408113;179408112
Novex-2	23323	70192;70193;70194	chr2:178543387;178543386;178543385	chr2:179408114;179408113;179408112
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-122
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.207
• 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
A/P	None	None	0.06	N	0.427	0.19	0.223847106136	gnomAD-4.0.0	3.42095E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49724E-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
A/C	0.5623	ambiguous	0.5336	ambiguous	-0.656	Destabilizing	1.0	D	0.724	deleterious	None	None	None	None	N
A/D	0.8233	likely_pathogenic	0.7936	pathogenic	-0.927	Destabilizing	0.99	D	0.718	prob.delet.	None	None	None	None	N
A/E	0.6945	likely_pathogenic	0.676	pathogenic	-0.979	Destabilizing	0.986	D	0.707	prob.delet.	N	0.486875692	None	None	N
A/F	0.7028	likely_pathogenic	0.6552	pathogenic	-0.996	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
A/G	0.2488	likely_benign	0.2232	benign	-1.06	Destabilizing	0.953	D	0.565	neutral	N	0.487945251	None	None	N
A/H	0.818	likely_pathogenic	0.7969	pathogenic	-1.184	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
A/I	0.4719	ambiguous	0.4174	ambiguous	-0.359	Destabilizing	0.995	D	0.757	deleterious	None	None	None	None	N
A/K	0.8481	likely_pathogenic	0.8374	pathogenic	-1.05	Destabilizing	0.99	D	0.713	prob.delet.	None	None	None	None	N
A/L	0.4453	ambiguous	0.4103	ambiguous	-0.359	Destabilizing	0.982	D	0.663	prob.neutral	None	None	None	None	N
A/M	0.4231	ambiguous	0.3918	ambiguous	-0.198	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
A/N	0.609	likely_pathogenic	0.5768	pathogenic	-0.719	Destabilizing	0.99	D	0.845	deleterious	None	None	None	None	N
A/P	0.1577	likely_benign	0.155	benign	-0.474	Destabilizing	0.06	N	0.427	neutral	N	0.379932352	None	None	N
A/Q	0.6955	likely_pathogenic	0.6793	pathogenic	-0.902	Destabilizing	0.995	D	0.739	deleterious	None	None	None	None	N
A/R	0.7854	likely_pathogenic	0.7731	pathogenic	-0.666	Destabilizing	0.995	D	0.759	deleterious	None	None	None	None	N
A/S	0.1479	likely_benign	0.1337	benign	-1.061	Destabilizing	0.647	D	0.378	neutral	N	0.42789687	None	None	N
A/T	0.1921	likely_benign	0.1741	benign	-1.023	Destabilizing	0.91	D	0.691	prob.delet.	N	0.488963971	None	None	N
A/V	0.2371	likely_benign	0.2047	benign	-0.474	Destabilizing	0.976	D	0.698	prob.delet.	N	0.476936037	None	None	N
A/W	0.9342	likely_pathogenic	0.9192	pathogenic	-1.317	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
A/Y	0.7996	likely_pathogenic	0.7704	pathogenic	-0.92	Destabilizing	0.998	D	0.831	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.