TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8365	25318;25319;25320	chr2:178717781;178717780;178717779	chr2:179582508;179582507;179582506
N2AB	8048	24367;24368;24369	chr2:178717781;178717780;178717779	chr2:179582508;179582507;179582506
N2A	7121	21586;21587;21588	chr2:178717781;178717780;178717779	chr2:179582508;179582507;179582506
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-69
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6185
• 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
K/N	rs2077715561	None	0.999	N	0.622	0.367	0.268660756437	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs2077715561	None	0.999	N	0.622	0.367	0.268660756437	gnomAD-4.0.0	6.84128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.34602E-06	0	0
K/T	rs2077715930	None	0.998	D	0.659	0.405	0.53787198782	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92827E-04	None	0	0	0	0	0
K/T	rs2077715930	None	0.998	D	0.659	0.405	0.53787198782	gnomAD-4.0.0	5.16261E-06	None	None	None	None	N	None	0	0	None	0	2.42966E-05	None	0	0	0	0	8.60486E-05

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
K/A	0.3777	ambiguous	0.4292	ambiguous	-0.398	Destabilizing	0.996	D	0.621	neutral	None	None	None	None	N
K/C	0.8204	likely_pathogenic	0.8457	pathogenic	-0.473	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
K/D	0.5658	likely_pathogenic	0.6363	pathogenic	0.414	Stabilizing	0.999	D	0.663	neutral	None	None	None	None	N
K/E	0.2046	likely_benign	0.2364	benign	0.501	Stabilizing	0.983	D	0.579	neutral	N	0.508566531	None	None	N
K/F	0.8097	likely_pathogenic	0.8447	pathogenic	-0.217	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
K/G	0.5106	ambiguous	0.5693	pathogenic	-0.703	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	N
K/H	0.335	likely_benign	0.3665	ambiguous	-0.839	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/I	0.4318	ambiguous	0.4797	ambiguous	0.363	Stabilizing	0.992	D	0.751	deleterious	N	0.506710327	None	None	N
K/L	0.4141	ambiguous	0.4678	ambiguous	0.363	Stabilizing	0.981	D	0.641	neutral	None	None	None	None	N
K/M	0.2806	likely_benign	0.3193	benign	0.06	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
K/N	0.4041	ambiguous	0.4455	ambiguous	-0.081	Destabilizing	0.999	D	0.622	neutral	N	0.485607559	None	None	N
K/P	0.3774	ambiguous	0.4211	ambiguous	0.139	Stabilizing	0.441	N	0.369	neutral	None	None	None	None	N
K/Q	0.1389	likely_benign	0.1527	benign	-0.138	Destabilizing	0.988	D	0.625	neutral	N	0.490962205	None	None	N
K/R	0.0973	likely_benign	0.1056	benign	-0.201	Destabilizing	0.203	N	0.333	neutral	D	0.522823908	None	None	N
K/S	0.431	ambiguous	0.48	ambiguous	-0.76	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
K/T	0.1865	likely_benign	0.2098	benign	-0.477	Destabilizing	0.998	D	0.659	neutral	D	0.525517496	None	None	N
K/V	0.3926	ambiguous	0.44	ambiguous	0.139	Stabilizing	0.986	D	0.655	neutral	None	None	None	None	N
K/W	0.8257	likely_pathogenic	0.863	pathogenic	-0.113	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/Y	0.6705	likely_pathogenic	0.7202	pathogenic	0.178	Stabilizing	0.996	D	0.73	prob.delet.	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.