TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8659	26200;26201;26202	chr2:178715211;178715210;178715209	chr2:179579938;179579937;179579936
N2AB	8342	25249;25250;25251	chr2:178715211;178715210;178715209	chr2:179579938;179579937;179579936
N2A	7415	22468;22469;22470	chr2:178715211;178715210;178715209	chr2:179579938;179579937;179579936
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-72
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3677
• 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/N	rs774443573	-0.845	0.992	N	0.685	0.241	0.139678290688	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
D/N	rs774443573	-0.845	0.992	N	0.685	0.241	0.139678290688	gnomAD-4.0.0	4.77512E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57751E-06	0	0
D/V	rs1276014518	0.258	0.997	N	0.835	0.389	0.447609009685	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
D/V	rs1276014518	0.258	0.997	N	0.835	0.389	0.447609009685	gnomAD-4.0.0	6.36659E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14365E-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
D/A	0.3552	ambiguous	0.3038	benign	-0.427	Destabilizing	0.996	D	0.717	prob.delet.	N	0.500884758	None	None	N
D/C	0.9061	likely_pathogenic	0.8688	pathogenic	-0.124	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
D/E	0.3156	likely_benign	0.3	benign	-0.568	Destabilizing	0.026	N	0.31	neutral	N	0.468502981	None	None	N
D/F	0.8639	likely_pathogenic	0.8382	pathogenic	-0.231	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
D/G	0.4591	ambiguous	0.4131	ambiguous	-0.71	Destabilizing	0.982	D	0.725	prob.delet.	N	0.485343712	None	None	N
D/H	0.6326	likely_pathogenic	0.5885	pathogenic	-0.403	Destabilizing	1.0	D	0.793	deleterious	N	0.474747875	None	None	N
D/I	0.7212	likely_pathogenic	0.6519	pathogenic	0.293	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
D/K	0.7895	likely_pathogenic	0.7535	pathogenic	-0.196	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
D/L	0.7356	likely_pathogenic	0.6894	pathogenic	0.293	Stabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
D/M	0.8581	likely_pathogenic	0.8313	pathogenic	0.596	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
D/N	0.2049	likely_benign	0.1874	benign	-0.527	Destabilizing	0.992	D	0.685	prob.neutral	N	0.469407058	None	None	N
D/P	0.856	likely_pathogenic	0.808	pathogenic	0.077	Stabilizing	0.981	D	0.819	deleterious	None	None	None	None	N
D/Q	0.697	likely_pathogenic	0.663	pathogenic	-0.436	Destabilizing	0.996	D	0.744	deleterious	None	None	None	None	N
D/R	0.7965	likely_pathogenic	0.7641	pathogenic	-0.016	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
D/S	0.2581	likely_benign	0.2188	benign	-0.692	Destabilizing	0.99	D	0.653	neutral	None	None	None	None	N
D/T	0.5012	ambiguous	0.4431	ambiguous	-0.473	Destabilizing	0.994	D	0.797	deleterious	None	None	None	None	N
D/V	0.4891	ambiguous	0.4209	ambiguous	0.077	Stabilizing	0.997	D	0.835	deleterious	N	0.514526059	None	None	N
D/W	0.9723	likely_pathogenic	0.9684	pathogenic	-0.095	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
D/Y	0.5383	ambiguous	0.5029	ambiguous	-0.015	Destabilizing	1.0	D	0.831	deleterious	N	0.48610418	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.