TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8083	24472;24473;24474	chr2:178718953;178718952;178718951	chr2:179583680;179583679;179583678
N2AB	7766	23521;23522;23523	chr2:178718953;178718952;178718951	chr2:179583680;179583679;179583678
N2A	6839	20740;20741;20742	chr2:178718953;178718952;178718951	chr2:179583680;179583679;179583678
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-66
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5475
• 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/S	None	None	0.012	N	0.224	0.057	0.0138822411134	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.0816	likely_benign	0.0819	benign	-0.973	Destabilizing	None	N	0.073	neutral	N	0.452258619	None	None	N
T/C	0.4749	ambiguous	0.462	ambiguous	-0.498	Destabilizing	0.676	D	0.323	neutral	None	None	None	None	N
T/D	0.3806	ambiguous	0.3711	ambiguous	-0.167	Destabilizing	0.072	N	0.317	neutral	None	None	None	None	N
T/E	0.183	likely_benign	0.1849	benign	-0.188	Destabilizing	0.016	N	0.317	neutral	None	None	None	None	N
T/F	0.1787	likely_benign	0.1742	benign	-1.156	Destabilizing	0.214	N	0.387	neutral	None	None	None	None	N
T/G	0.2881	likely_benign	0.2839	benign	-1.199	Destabilizing	0.016	N	0.349	neutral	None	None	None	None	N
T/H	0.1917	likely_benign	0.2007	benign	-1.523	Destabilizing	0.356	N	0.34	neutral	None	None	None	None	N
T/I	0.0894	likely_benign	0.0928	benign	-0.464	Destabilizing	None	N	0.221	neutral	N	0.498401813	None	None	N
T/K	0.0817	likely_benign	0.0889	benign	-0.712	Destabilizing	None	N	0.168	neutral	None	None	None	None	N
T/L	0.0723	likely_benign	0.0716	benign	-0.464	Destabilizing	0.006	N	0.333	neutral	None	None	None	None	N
T/M	0.063	likely_benign	0.062	benign	-0.038	Destabilizing	0.214	N	0.331	neutral	None	None	None	None	N
T/N	0.1267	likely_benign	0.1209	benign	-0.533	Destabilizing	0.055	N	0.266	neutral	N	0.454269628	None	None	N
T/P	0.0945	likely_benign	0.0957	benign	-0.604	Destabilizing	None	N	0.124	neutral	N	0.443412535	None	None	N
T/Q	0.1314	likely_benign	0.1364	benign	-0.776	Destabilizing	0.003	N	0.201	neutral	None	None	None	None	N
T/R	0.0901	likely_benign	0.0928	benign	-0.46	Destabilizing	0.038	N	0.384	neutral	None	None	None	None	N
T/S	0.1234	likely_benign	0.1215	benign	-0.85	Destabilizing	0.012	N	0.224	neutral	N	0.499361818	None	None	N
T/V	0.0953	likely_benign	0.0971	benign	-0.604	Destabilizing	None	N	0.087	neutral	None	None	None	None	N
T/W	0.5097	ambiguous	0.5026	ambiguous	-1.032	Destabilizing	0.864	D	0.357	neutral	None	None	None	None	N
T/Y	0.2225	likely_benign	0.2195	benign	-0.82	Destabilizing	0.356	N	0.359	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.