TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6645	20158;20159;20160	chr2:178727645;178727644;178727643	chr2:179592372;179592371;179592370
N2AB	6328	19207;19208;19209	chr2:178727645;178727644;178727643	chr2:179592372;179592371;179592370
N2A	5401	16426;16427;16428	chr2:178727645;178727644;178727643	chr2:179592372;179592371;179592370
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-50
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.2049
• 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
T/A	rs370671112	-1.186	0.925	N	0.615	0.258	None	gnomAD-2.1.1	2.54E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.4E-05	None	0	4.74E-05	0
T/A	rs370671112	-1.186	0.925	N	0.615	0.258	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
T/A	rs370671112	-1.186	0.925	N	0.615	0.258	None	gnomAD-4.0.0	2.36301E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.05744E-05	1.11349E-05	1.60658E-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
T/A	0.0993	likely_benign	0.106	benign	-1.02	Destabilizing	0.925	D	0.615	neutral	N	0.473661919	None	None	N
T/C	0.4808	ambiguous	0.483	ambiguous	-0.693	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
T/D	0.491	ambiguous	0.5416	ambiguous	-1.822	Destabilizing	0.997	D	0.72	prob.delet.	None	None	None	None	N
T/E	0.3762	ambiguous	0.4333	ambiguous	-1.602	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/F	0.2456	likely_benign	0.2611	benign	-0.69	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
T/G	0.3437	ambiguous	0.3902	ambiguous	-1.428	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
T/H	0.2219	likely_benign	0.2445	benign	-1.608	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/I	0.1296	likely_benign	0.1503	benign	0.059	Stabilizing	1.0	D	0.761	deleterious	N	0.463279892	None	None	N
T/K	0.176	likely_benign	0.2022	benign	-0.316	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/L	0.1181	likely_benign	0.1346	benign	0.059	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
T/M	0.1022	likely_benign	0.1082	benign	0.008	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
T/N	0.1621	likely_benign	0.1693	benign	-1.147	Destabilizing	0.996	D	0.697	prob.neutral	N	0.504136438	None	None	N
T/P	0.7227	likely_pathogenic	0.7838	pathogenic	-0.271	Destabilizing	0.998	D	0.763	deleterious	N	0.515910817	None	None	N
T/Q	0.2216	likely_benign	0.2497	benign	-0.849	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
T/R	0.1244	likely_benign	0.1461	benign	-0.663	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/S	0.1143	likely_benign	0.1167	benign	-1.272	Destabilizing	0.477	N	0.345	neutral	N	0.462137156	None	None	N
T/V	0.1255	likely_benign	0.1412	benign	-0.271	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	N
T/W	0.608	likely_pathogenic	0.6581	pathogenic	-0.989	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
T/Y	0.2893	likely_benign	0.3114	benign	-0.554	Destabilizing	1.0	D	0.811	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.