TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8621	26086;26087;26088	chr2:178715553;178715552;178715551	chr2:179580280;179580279;179580278
N2AB	8304	25135;25136;25137	chr2:178715553;178715552;178715551	chr2:179580280;179580279;179580278
N2A	7377	22354;22355;22356	chr2:178715553;178715552;178715551	chr2:179580280;179580279;179580278
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-71
• Domain position: 73
• Structural Position: 155
• Q(SASA): 0.1961
• 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/I	None	None	0.998	N	0.763	0.229	0.406668915854	gnomAD-4.0.0	6.84286E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9957E-07	0	0
T/N	rs899151063	-1.338	0.98	N	0.72	0.314	0.381071309025	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
T/N	rs899151063	-1.338	0.98	N	0.72	0.314	0.381071309025	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
T/N	rs899151063	-1.338	0.98	N	0.72	0.314	0.381071309025	gnomAD-4.0.0	4.33843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93395E-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
T/A	0.1283	likely_benign	0.1151	benign	-1.355	Destabilizing	0.489	N	0.593	neutral	N	0.482220294	None	None	N
T/C	0.5492	ambiguous	0.4867	ambiguous	-0.922	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/D	0.7267	likely_pathogenic	0.7087	pathogenic	-1.267	Destabilizing	0.985	D	0.734	prob.delet.	None	None	None	None	N
T/E	0.6056	likely_pathogenic	0.5704	pathogenic	-1.065	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
T/F	0.275	likely_benign	0.2412	benign	-1.136	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
T/G	0.4456	ambiguous	0.4348	ambiguous	-1.751	Destabilizing	0.988	D	0.683	prob.neutral	None	None	None	None	N
T/H	0.319	likely_benign	0.2941	benign	-1.751	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
T/I	0.1386	likely_benign	0.1038	benign	-0.311	Destabilizing	0.998	D	0.763	deleterious	N	0.494076216	None	None	N
T/K	0.3435	ambiguous	0.2923	benign	-0.262	Destabilizing	0.997	D	0.731	prob.delet.	None	None	None	None	N
T/L	0.1263	likely_benign	0.1041	benign	-0.311	Destabilizing	0.989	D	0.663	neutral	None	None	None	None	N
T/M	0.1051	likely_benign	0.1015	benign	-0.311	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
T/N	0.2526	likely_benign	0.2491	benign	-0.92	Destabilizing	0.98	D	0.72	prob.delet.	N	0.512859397	None	None	N
T/P	0.821	likely_pathogenic	0.7514	pathogenic	-0.63	Destabilizing	0.99	D	0.767	deleterious	D	0.524469192	None	None	N
T/Q	0.3639	ambiguous	0.3253	benign	-0.758	Destabilizing	0.997	D	0.781	deleterious	None	None	None	None	N
T/R	0.2299	likely_benign	0.1927	benign	-0.465	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
T/S	0.1551	likely_benign	0.1519	benign	-1.247	Destabilizing	0.058	N	0.429	neutral	N	0.492035988	None	None	N
T/V	0.137	likely_benign	0.1143	benign	-0.63	Destabilizing	0.984	D	0.591	neutral	None	None	None	None	N
T/W	0.6472	likely_pathogenic	0.6142	pathogenic	-1.17	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
T/Y	0.3222	likely_benign	0.3083	benign	-0.81	Destabilizing	1.0	D	0.843	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.