TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22776	68551;68552;68553	chr2:178578614;178578613;178578612	chr2:179443341;179443340;179443339
N2AB	21135	63628;63629;63630	chr2:178578614;178578613;178578612	chr2:179443341;179443340;179443339
N2A	20208	60847;60848;60849	chr2:178578614;178578613;178578612	chr2:179443341;179443340;179443339
N2B	13711	41356;41357;41358	chr2:178578614;178578613;178578612	chr2:179443341;179443340;179443339
Novex-1	13836	41731;41732;41733	chr2:178578614;178578613;178578612	chr2:179443341;179443340;179443339
Novex-2	13903	41932;41933;41934	chr2:178578614;178578613;178578612	chr2:179443341;179443340;179443339
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-53
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3345
• Predicted PPI site: I

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	rs1347609224	None	1.0	N	0.841	0.459	0.366848117066	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1347609224	None	1.0	N	0.841	0.459	0.366848117066	gnomAD-4.0.0	6.57782E-06	None	None	None	None	I	None	2.41464E-05	0	None	0	0	None	0	0	0	0	0
T/R	None	None	1.0	N	0.842	0.47	0.463843524616	gnomAD-4.0.0	1.20373E-06	None	None	None	None	I	None	0	1.01833E-03	None	0	0	None	0	0	0	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	0.1778	likely_benign	0.1587	benign	-0.568	Destabilizing	0.999	D	0.569	neutral	N	0.482893355	None	None	I
T/C	0.5476	ambiguous	0.526	ambiguous	-0.357	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
T/D	0.8178	likely_pathogenic	0.817	pathogenic	0.267	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
T/E	0.6848	likely_pathogenic	0.6852	pathogenic	0.259	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
T/F	0.4206	ambiguous	0.4065	ambiguous	-0.683	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
T/G	0.5076	ambiguous	0.4514	ambiguous	-0.806	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
T/H	0.5258	ambiguous	0.5233	ambiguous	-1.044	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
T/I	0.1934	likely_benign	0.1876	benign	-0.037	Destabilizing	1.0	D	0.841	deleterious	N	0.444794694	None	None	I
T/K	0.513	ambiguous	0.5385	ambiguous	-0.517	Destabilizing	1.0	D	0.843	deleterious	N	0.489084188	None	None	I
T/L	0.1101	likely_benign	0.1105	benign	-0.037	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
T/M	0.1011	likely_benign	0.0981	benign	0.06	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
T/N	0.3058	likely_benign	0.2879	benign	-0.412	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
T/P	0.7472	likely_pathogenic	0.7189	pathogenic	-0.182	Destabilizing	1.0	D	0.839	deleterious	N	0.520876292	None	None	I
T/Q	0.4372	ambiguous	0.4299	ambiguous	-0.524	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
T/R	0.4522	ambiguous	0.4821	ambiguous	-0.339	Destabilizing	1.0	D	0.842	deleterious	N	0.520311173	None	None	I
T/S	0.2058	likely_benign	0.1806	benign	-0.706	Destabilizing	0.999	D	0.566	neutral	N	0.503552209	None	None	I
T/V	0.1591	likely_benign	0.1525	benign	-0.182	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	I
T/W	0.7967	likely_pathogenic	0.8027	pathogenic	-0.658	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
T/Y	0.538	ambiguous	0.5403	ambiguous	-0.407	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I

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.