TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31228	93907;93908;93909	chr2:178547944;178547943;178547942	chr2:179412671;179412670;179412669
N2AB	29587	88984;88985;88986	chr2:178547944;178547943;178547942	chr2:179412671;179412670;179412669
N2A	28660	86203;86204;86205	chr2:178547944;178547943;178547942	chr2:179412671;179412670;179412669
N2B	22163	66712;66713;66714	chr2:178547944;178547943;178547942	chr2:179412671;179412670;179412669
Novex-1	22288	67087;67088;67089	chr2:178547944;178547943;178547942	chr2:179412671;179412670;179412669
Novex-2	22355	67288;67289;67290	chr2:178547944;178547943;178547942	chr2:179412671;179412670;179412669
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-151
• Domain position: 11
• Structural Position: 18
• Q(SASA): 0.7933
• Predicted PPI site: I

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
K/R	rs368714667	0.184	0.928	N	0.613	0.185	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/R	rs368714667	0.184	0.928	N	0.613	0.185	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/R	rs368714667	0.184	0.928	N	0.613	0.185	None	gnomAD-4.0.0	3.40838E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.66174E-05	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
K/A	0.8335	likely_pathogenic	0.8207	pathogenic	-0.117	Destabilizing	0.944	D	0.681	prob.neutral	None	None	None	None	I
K/C	0.9275	likely_pathogenic	0.9182	pathogenic	-0.292	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	I
K/D	0.952	likely_pathogenic	0.9463	pathogenic	0.103	Stabilizing	0.968	D	0.646	neutral	None	None	None	None	I
K/E	0.6971	likely_pathogenic	0.6615	pathogenic	0.108	Stabilizing	0.928	D	0.63	neutral	N	0.484313658	None	None	I
K/F	0.9586	likely_pathogenic	0.9464	pathogenic	-0.367	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	I
K/G	0.8895	likely_pathogenic	0.8888	pathogenic	-0.311	Destabilizing	0.895	D	0.652	neutral	None	None	None	None	I
K/H	0.6259	likely_pathogenic	0.5777	pathogenic	-0.601	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	I
K/I	0.7805	likely_pathogenic	0.744	pathogenic	0.313	Stabilizing	0.989	D	0.717	prob.delet.	N	0.490202688	None	None	I
K/L	0.7038	likely_pathogenic	0.6851	pathogenic	0.313	Stabilizing	0.992	D	0.631	neutral	None	None	None	None	I
K/M	0.6559	likely_pathogenic	0.624	pathogenic	0.192	Stabilizing	0.999	D	0.661	neutral	None	None	None	None	I
K/N	0.9162	likely_pathogenic	0.9021	pathogenic	0.137	Stabilizing	0.085	N	0.398	neutral	N	0.503178381	None	None	I
K/P	0.8578	likely_pathogenic	0.847	pathogenic	0.197	Stabilizing	0.992	D	0.661	neutral	None	None	None	None	I
K/Q	0.3658	ambiguous	0.3379	benign	-0.05	Destabilizing	0.978	D	0.677	prob.neutral	N	0.493517143	None	None	I
K/R	0.0894	likely_benign	0.0881	benign	-0.063	Destabilizing	0.928	D	0.613	neutral	N	0.453905327	None	None	I
K/S	0.8974	likely_pathogenic	0.8826	pathogenic	-0.392	Destabilizing	0.895	D	0.65	neutral	None	None	None	None	I
K/T	0.6655	likely_pathogenic	0.6381	pathogenic	-0.235	Destabilizing	0.978	D	0.637	neutral	N	0.483174796	None	None	I
K/V	0.7326	likely_pathogenic	0.7078	pathogenic	0.197	Stabilizing	0.992	D	0.699	prob.neutral	None	None	None	None	I
K/W	0.9471	likely_pathogenic	0.9297	pathogenic	-0.356	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	I
K/Y	0.9082	likely_pathogenic	0.8842	pathogenic	-0.001	Destabilizing	0.997	D	0.701	prob.neutral	None	None	None	None	I

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.