TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10027	30304;30305;30306	chr2:178704291;178704290;178704289	chr2:179569018;179569017;179569016
N2AB	9710	29353;29354;29355	chr2:178704291;178704290;178704289	chr2:179569018;179569017;179569016
N2A	8783	26572;26573;26574	chr2:178704291;178704290;178704289	chr2:179569018;179569017;179569016
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-85
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.3965
• 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
I/L	None	None	None	None	0.103	0.086	0.31077124679	gnomAD-4.0.0	1.59086E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
I/T	rs751219454	-0.865	0.007	None	0.297	0.08	0.597704877147	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
I/T	rs751219454	-0.865	0.007	None	0.297	0.08	0.597704877147	gnomAD-4.0.0	1.59087E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8575E-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
I/A	0.3041	likely_benign	0.4066	ambiguous	-1.241	Destabilizing	None	N	0.133	neutral	None	None	None	None	N
I/C	0.6887	likely_pathogenic	0.7824	pathogenic	-0.703	Destabilizing	0.245	N	0.314	neutral	None	None	None	None	N
I/D	0.6598	likely_pathogenic	0.7471	pathogenic	-0.592	Destabilizing	0.044	N	0.459	neutral	None	None	None	None	N
I/E	0.4611	ambiguous	0.5262	ambiguous	-0.583	Destabilizing	0.009	N	0.381	neutral	None	None	None	None	N
I/F	0.1718	likely_benign	0.1953	benign	-0.76	Destabilizing	0.017	N	0.231	neutral	None	None	None	None	N
I/G	0.6304	likely_pathogenic	0.7696	pathogenic	-1.541	Destabilizing	0.009	N	0.374	neutral	None	None	None	None	N
I/H	0.3832	ambiguous	0.4741	ambiguous	-0.681	Destabilizing	0.138	N	0.417	neutral	None	None	None	None	N
I/K	0.2278	likely_benign	0.2907	benign	-0.826	Destabilizing	0.009	N	0.337	neutral	None	None	None	None	N
I/L	0.0844	likely_benign	0.1066	benign	-0.503	Destabilizing	None	N	0.103	neutral	None	None	None	None	N
I/M	0.102	likely_benign	0.1225	benign	-0.491	Destabilizing	0.057	N	0.282	neutral	None	None	None	None	N
I/N	0.2301	likely_benign	0.298	benign	-0.693	Destabilizing	0.065	N	0.481	neutral	None	None	None	None	N
I/P	0.3565	ambiguous	0.4589	ambiguous	-0.717	Destabilizing	None	N	0.231	neutral	None	None	None	None	N
I/Q	0.3076	likely_benign	0.4002	ambiguous	-0.815	Destabilizing	0.002	N	0.275	neutral	None	None	None	None	N
I/R	0.1936	likely_benign	0.2456	benign	-0.297	Destabilizing	None	N	0.251	neutral	None	None	None	None	N
I/S	0.2916	likely_benign	0.3831	ambiguous	-1.262	Destabilizing	0.007	N	0.291	neutral	None	None	None	None	N
I/T	0.2654	likely_benign	0.3541	ambiguous	-1.136	Destabilizing	0.007	N	0.297	neutral	None	None	None	None	N
I/V	0.0868	likely_benign	0.1051	benign	-0.717	Destabilizing	None	N	0.116	neutral	None	None	None	None	N
I/W	0.7101	likely_pathogenic	0.7573	pathogenic	-0.851	Destabilizing	0.55	D	0.393	neutral	None	None	None	None	N
I/Y	0.4371	ambiguous	0.4983	ambiguous	-0.611	Destabilizing	None	N	0.218	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.