TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26498	79717;79718;79719	chr2:178566640;178566639;178566638	chr2:179431367;179431366;179431365
N2AB	24857	74794;74795;74796	chr2:178566640;178566639;178566638	chr2:179431367;179431366;179431365
N2A	23930	72013;72014;72015	chr2:178566640;178566639;178566638	chr2:179431367;179431366;179431365
N2B	17433	52522;52523;52524	chr2:178566640;178566639;178566638	chr2:179431367;179431366;179431365
Novex-1	17558	52897;52898;52899	chr2:178566640;178566639;178566638	chr2:179431367;179431366;179431365
Novex-2	17625	53098;53099;53100	chr2:178566640;178566639;178566638	chr2:179431367;179431366;179431365
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-81
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3976
• 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
D/H	rs1705981523	None	1.0	N	0.621	0.538	0.356484672536	gnomAD-4.0.0	1.36926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79907E-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
D/A	0.8699	likely_pathogenic	0.8394	pathogenic	-0.457	Destabilizing	1.0	D	0.697	prob.neutral	N	0.46625345	None	None	N
D/C	0.9859	likely_pathogenic	0.9781	pathogenic	0.023	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	N
D/E	0.8157	likely_pathogenic	0.775	pathogenic	-0.591	Destabilizing	1.0	D	0.393	neutral	N	0.480133844	None	None	N
D/F	0.9843	likely_pathogenic	0.9745	pathogenic	-0.522	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
D/G	0.8174	likely_pathogenic	0.7844	pathogenic	-0.697	Destabilizing	1.0	D	0.702	prob.neutral	N	0.492119612	None	None	N
D/H	0.9511	likely_pathogenic	0.9349	pathogenic	-0.725	Destabilizing	1.0	D	0.621	neutral	N	0.504187161	None	None	N
D/I	0.9841	likely_pathogenic	0.9709	pathogenic	0.137	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
D/K	0.9798	likely_pathogenic	0.9706	pathogenic	0.018	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
D/L	0.9668	likely_pathogenic	0.9536	pathogenic	0.137	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
D/M	0.9897	likely_pathogenic	0.9831	pathogenic	0.523	Stabilizing	1.0	D	0.635	neutral	None	None	None	None	N
D/N	0.534	ambiguous	0.4755	ambiguous	-0.249	Destabilizing	1.0	D	0.647	neutral	N	0.470683995	None	None	N
D/P	0.9985	likely_pathogenic	0.9972	pathogenic	-0.038	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
D/Q	0.9654	likely_pathogenic	0.9526	pathogenic	-0.217	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
D/R	0.9751	likely_pathogenic	0.9657	pathogenic	0.052	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
D/S	0.7217	likely_pathogenic	0.6657	pathogenic	-0.391	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
D/T	0.9248	likely_pathogenic	0.8819	pathogenic	-0.207	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
D/V	0.9489	likely_pathogenic	0.917	pathogenic	-0.038	Destabilizing	1.0	D	0.728	prob.delet.	N	0.498146773	None	None	N
D/W	0.9973	likely_pathogenic	0.9953	pathogenic	-0.425	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
D/Y	0.9065	likely_pathogenic	0.8704	pathogenic	-0.3	Destabilizing	1.0	D	0.628	neutral	N	0.499414221	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.