TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31174	93745;93746;93747	chr2:178548106;178548105;178548104	chr2:179412833;179412832;179412831
N2AB	29533	88822;88823;88824	chr2:178548106;178548105;178548104	chr2:179412833;179412832;179412831
N2A	28606	86041;86042;86043	chr2:178548106;178548105;178548104	chr2:179412833;179412832;179412831
N2B	22109	66550;66551;66552	chr2:178548106;178548105;178548104	chr2:179412833;179412832;179412831
Novex-1	22234	66925;66926;66927	chr2:178548106;178548105;178548104	chr2:179412833;179412832;179412831
Novex-2	22301	67126;67127;67128	chr2:178548106;178548105;178548104	chr2:179412833;179412832;179412831
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-115
• Domain position: 62
• Structural Position: 94
• Q(SASA): 0.6745
• 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/G	None	None	0.477	N	0.58	0.327	0.300784259202	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
E/A	0.1613	likely_benign	0.1593	benign	-0.622	Destabilizing	0.645	D	0.596	neutral	N	0.473229302	None	None	N
E/C	0.7819	likely_pathogenic	0.8075	pathogenic	-0.179	Destabilizing	0.995	D	0.69	prob.neutral	None	None	None	None	N
E/D	0.0896	likely_benign	0.097	benign	-0.442	Destabilizing	0.006	N	0.245	neutral	N	0.418914814	None	None	N
E/F	0.7558	likely_pathogenic	0.7743	pathogenic	-0.297	Destabilizing	0.995	D	0.698	prob.neutral	None	None	None	None	N
E/G	0.1225	likely_benign	0.1169	benign	-0.851	Destabilizing	0.477	N	0.58	neutral	N	0.463609741	None	None	N
E/H	0.3851	ambiguous	0.3846	ambiguous	-0.109	Destabilizing	0.945	D	0.615	neutral	None	None	None	None	N
E/I	0.4728	ambiguous	0.4955	ambiguous	-0.037	Destabilizing	0.945	D	0.717	prob.delet.	None	None	None	None	N
E/K	0.1537	likely_benign	0.1436	benign	0.267	Stabilizing	0.645	D	0.551	neutral	N	0.394075085	None	None	N
E/L	0.4124	ambiguous	0.4244	ambiguous	-0.037	Destabilizing	0.945	D	0.699	prob.neutral	None	None	None	None	N
E/M	0.5064	ambiguous	0.5217	ambiguous	0.13	Stabilizing	0.995	D	0.68	prob.neutral	None	None	None	None	N
E/N	0.1811	likely_benign	0.1915	benign	-0.253	Destabilizing	0.017	N	0.316	neutral	None	None	None	None	N
E/P	0.3489	ambiguous	0.3489	ambiguous	-0.212	Destabilizing	0.945	D	0.69	prob.neutral	None	None	None	None	N
E/Q	0.1357	likely_benign	0.132	benign	-0.19	Destabilizing	0.864	D	0.589	neutral	N	0.455296902	None	None	N
E/R	0.2645	likely_benign	0.2449	benign	0.497	Stabilizing	0.894	D	0.601	neutral	None	None	None	None	N
E/S	0.1479	likely_benign	0.1519	benign	-0.398	Destabilizing	0.547	D	0.537	neutral	None	None	None	None	N
E/T	0.1793	likely_benign	0.1872	benign	-0.197	Destabilizing	0.707	D	0.621	neutral	None	None	None	None	N
E/V	0.2885	likely_benign	0.2994	benign	-0.212	Destabilizing	0.928	D	0.683	prob.neutral	N	0.459492	None	None	N
E/W	0.8636	likely_pathogenic	0.8561	pathogenic	-0.041	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
E/Y	0.6143	likely_pathogenic	0.6172	pathogenic	-0.027	Destabilizing	0.981	D	0.699	prob.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.