TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26532	79819;79820;79821	chr2:178566538;178566537;178566536	chr2:179431265;179431264;179431263
N2AB	24891	74896;74897;74898	chr2:178566538;178566537;178566536	chr2:179431265;179431264;179431263
N2A	23964	72115;72116;72117	chr2:178566538;178566537;178566536	chr2:179431265;179431264;179431263
N2B	17467	52624;52625;52626	chr2:178566538;178566537;178566536	chr2:179431265;179431264;179431263
Novex-1	17592	52999;53000;53001	chr2:178566538;178566537;178566536	chr2:179431265;179431264;179431263
Novex-2	17659	53200;53201;53202	chr2:178566538;178566537;178566536	chr2:179431265;179431264;179431263
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-81
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9384
• 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
E/K	rs964829504	0.633	0.645	N	0.557	0.284	0.315314060047	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
E/K	rs964829504	0.633	0.645	N	0.557	0.284	0.315314060047	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/K	rs964829504	0.633	0.645	N	0.557	0.284	0.315314060047	gnomAD-4.0.0	3.09936E-06	None	None	None	None	N	None	0	5.00384E-05	None	0	0	None	0	3.28839E-04	0	0	0
E/Q	None	None	0.864	N	0.526	0.285	0.339316883193	gnomAD-4.0.0	6.84392E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99522E-07	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
E/A	0.1117	likely_benign	0.1285	benign	-0.167	Destabilizing	0.645	D	0.551	neutral	N	0.47984863	None	None	N
E/C	0.6997	likely_pathogenic	0.7583	pathogenic	-0.244	Destabilizing	0.995	D	0.69	prob.neutral	None	None	None	None	N
E/D	0.072	likely_benign	0.0781	benign	-0.222	Destabilizing	0.002	N	0.401	neutral	N	0.446968207	None	None	N
E/F	0.6242	likely_pathogenic	0.6951	pathogenic	-0.087	Destabilizing	0.995	D	0.63	neutral	None	None	None	None	N
E/G	0.0991	likely_benign	0.1145	benign	-0.317	Destabilizing	0.645	D	0.455	neutral	N	0.464241672	None	None	N
E/H	0.3912	ambiguous	0.4852	ambiguous	0.474	Stabilizing	0.995	D	0.601	neutral	None	None	None	None	N
E/I	0.2465	likely_benign	0.3038	benign	0.181	Stabilizing	0.945	D	0.637	neutral	None	None	None	None	N
E/K	0.119	likely_benign	0.1549	benign	0.307	Stabilizing	0.645	D	0.557	neutral	N	0.476000248	None	None	N
E/L	0.2593	likely_benign	0.3102	benign	0.181	Stabilizing	0.945	D	0.622	neutral	None	None	None	None	N
E/M	0.3007	likely_benign	0.3488	ambiguous	-0.011	Destabilizing	0.995	D	0.597	neutral	None	None	None	None	N
E/N	0.144	likely_benign	0.1769	benign	0.037	Stabilizing	0.809	D	0.541	neutral	None	None	None	None	N
E/P	0.3186	likely_benign	0.4013	ambiguous	0.084	Stabilizing	0.945	D	0.553	neutral	None	None	None	None	N
E/Q	0.148	likely_benign	0.1761	benign	0.074	Stabilizing	0.864	D	0.526	neutral	N	0.517230795	None	None	N
E/R	0.2373	likely_benign	0.2981	benign	0.605	Stabilizing	0.894	D	0.584	neutral	None	None	None	None	N
E/S	0.1391	likely_benign	0.166	benign	-0.131	Destabilizing	0.547	D	0.555	neutral	None	None	None	None	N
E/T	0.1317	likely_benign	0.1578	benign	None	Stabilizing	0.894	D	0.534	neutral	None	None	None	None	N
E/V	0.1508	likely_benign	0.1797	benign	0.084	Stabilizing	0.928	D	0.569	neutral	N	0.472422423	None	None	N
E/W	0.8006	likely_pathogenic	0.8473	pathogenic	0.015	Stabilizing	0.995	D	0.697	prob.neutral	None	None	None	None	N
E/Y	0.4785	ambiguous	0.5554	ambiguous	0.146	Stabilizing	0.995	D	0.585	neutral	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.