TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14880	44863;44864;44865	chr2:178624642;178624641;178624640	chr2:179489369;179489368;179489367
N2AB	13239	39940;39941;39942	chr2:178624642;178624641;178624640	chr2:179489369;179489368;179489367
N2A	12312	37159;37160;37161	chr2:178624642;178624641;178624640	chr2:179489369;179489368;179489367
N2B	5815	17668;17669;17670	chr2:178624642;178624641;178624640	chr2:179489369;179489368;179489367
Novex-1	5940	18043;18044;18045	chr2:178624642;178624641;178624640	chr2:179489369;179489368;179489367
Novex-2	6007	18244;18245;18246	chr2:178624642;178624641;178624640	chr2:179489369;179489368;179489367
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-100
• Domain position: 28
• Structural Position: 43
• Q(SASA): 0.9235
• 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
N/S	rs747496717	0.283	0.822	N	0.551	0.201	0.236278675362	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66168E-04
N/S	rs747496717	0.283	0.822	N	0.551	0.201	0.236278675362	gnomAD-4.0.0	1.59382E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41896E-04	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
N/A	0.4888	ambiguous	0.4401	ambiguous	-0.112	Destabilizing	0.754	D	0.62	neutral	None	None	None	None	N
N/C	0.7838	likely_pathogenic	0.7535	pathogenic	0.264	Stabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
N/D	0.2021	likely_benign	0.1705	benign	0.132	Stabilizing	0.822	D	0.558	neutral	N	0.481511927	None	None	N
N/E	0.5306	ambiguous	0.4817	ambiguous	0.076	Stabilizing	0.86	D	0.548	neutral	None	None	None	None	N
N/F	0.7721	likely_pathogenic	0.7266	pathogenic	-0.648	Destabilizing	0.993	D	0.671	neutral	None	None	None	None	N
N/G	0.4676	ambiguous	0.4283	ambiguous	-0.229	Destabilizing	0.019	N	0.273	neutral	None	None	None	None	N
N/H	0.2389	likely_benign	0.2167	benign	-0.26	Destabilizing	0.99	D	0.535	neutral	D	0.550424452	None	None	N
N/I	0.5954	likely_pathogenic	0.499	ambiguous	0.098	Stabilizing	0.99	D	0.676	prob.neutral	N	0.502632639	None	None	N
N/K	0.4076	ambiguous	0.3673	ambiguous	0.141	Stabilizing	0.058	N	0.325	neutral	N	0.48369311	None	None	N
N/L	0.5104	ambiguous	0.4655	ambiguous	0.098	Stabilizing	0.978	D	0.641	neutral	None	None	None	None	N
N/M	0.5416	ambiguous	0.496	ambiguous	0.21	Stabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
N/P	0.889	likely_pathogenic	0.8299	pathogenic	0.053	Stabilizing	0.993	D	0.665	neutral	None	None	None	None	N
N/Q	0.5388	ambiguous	0.5129	ambiguous	-0.206	Destabilizing	0.956	D	0.537	neutral	None	None	None	None	N
N/R	0.6088	likely_pathogenic	0.5566	ambiguous	0.199	Stabilizing	0.915	D	0.513	neutral	None	None	None	None	N
N/S	0.2221	likely_benign	0.1943	benign	0.02	Stabilizing	0.822	D	0.551	neutral	N	0.476477603	None	None	N
N/T	0.2877	likely_benign	0.2408	benign	0.084	Stabilizing	0.904	D	0.528	neutral	N	0.497345096	None	None	N
N/V	0.591	likely_pathogenic	0.5134	ambiguous	0.053	Stabilizing	0.978	D	0.674	neutral	None	None	None	None	N
N/W	0.9298	likely_pathogenic	0.9035	pathogenic	-0.748	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
N/Y	0.3228	likely_benign	0.2795	benign	-0.432	Destabilizing	0.99	D	0.662	neutral	D	0.536602571	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.