TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15745	47458;47459;47460	chr2:178618225;178618224;178618223	chr2:179482952;179482951;179482950
N2AB	14104	42535;42536;42537	chr2:178618225;178618224;178618223	chr2:179482952;179482951;179482950
N2A	13177	39754;39755;39756	chr2:178618225;178618224;178618223	chr2:179482952;179482951;179482950
N2B	6680	20263;20264;20265	chr2:178618225;178618224;178618223	chr2:179482952;179482951;179482950
Novex-1	6805	20638;20639;20640	chr2:178618225;178618224;178618223	chr2:179482952;179482951;179482950
Novex-2	6872	20839;20840;20841	chr2:178618225;178618224;178618223	chr2:179482952;179482951;179482950
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: Fn3-1
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.2549
• 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	None	None	0.997	N	0.816	0.327	0.433600339574	gnomAD-4.0.0	3.42297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.4994E-06	0	0
E/V	rs1559848811	None	0.999	N	0.743	0.26	0.565205258651	gnomAD-4.0.0	6.84588E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99875E-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	0.2631	likely_benign	0.2086	benign	-0.663	Destabilizing	0.997	D	0.783	deleterious	N	0.473634178	None	None	N
E/C	0.9286	likely_pathogenic	0.8318	pathogenic	-0.354	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.493	ambiguous	0.411	ambiguous	-1.056	Destabilizing	0.997	D	0.75	deleterious	N	0.474999113	None	None	N
E/F	0.9185	likely_pathogenic	0.838	pathogenic	0.208	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/G	0.5137	ambiguous	0.4215	ambiguous	-1.086	Destabilizing	0.999	D	0.704	prob.delet.	N	0.499826492	None	None	N
E/H	0.8815	likely_pathogenic	0.7933	pathogenic	-0.01	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/I	0.5713	likely_pathogenic	0.3816	ambiguous	0.513	Stabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
E/K	0.5543	ambiguous	0.4436	ambiguous	-0.523	Destabilizing	0.997	D	0.816	deleterious	N	0.467912347	None	None	N
E/L	0.6404	likely_pathogenic	0.4866	ambiguous	0.513	Stabilizing	0.999	D	0.72	deleterious	None	None	None	None	N
E/M	0.6249	likely_pathogenic	0.4887	ambiguous	0.918	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/N	0.7227	likely_pathogenic	0.6001	pathogenic	-1.143	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
E/P	0.758	likely_pathogenic	0.6471	pathogenic	0.143	Stabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
E/Q	0.3382	likely_benign	0.2573	benign	-0.94	Destabilizing	0.999	D	0.776	deleterious	N	0.469046144	None	None	N
E/R	0.7234	likely_pathogenic	0.6047	pathogenic	-0.192	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/S	0.4848	ambiguous	0.3711	ambiguous	-1.51	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
E/T	0.4127	ambiguous	0.2878	benign	-1.145	Destabilizing	0.999	D	0.705	prob.delet.	None	None	None	None	N
E/V	0.3469	ambiguous	0.2204	benign	0.143	Stabilizing	0.999	D	0.743	deleterious	N	0.47856743	None	None	N
E/W	0.9837	likely_pathogenic	0.9592	pathogenic	0.494	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.9113	likely_pathogenic	0.8174	pathogenic	0.494	Stabilizing	1.0	D	0.847	deleterious	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.