TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17797	53614;53615;53616	chr2:178607213;178607212;178607211	chr2:179471940;179471939;179471938
N2AB	16156	48691;48692;48693	chr2:178607213;178607212;178607211	chr2:179471940;179471939;179471938
N2A	15229	45910;45911;45912	chr2:178607213;178607212;178607211	chr2:179471940;179471939;179471938
N2B	8732	26419;26420;26421	chr2:178607213;178607212;178607211	chr2:179471940;179471939;179471938
Novex-1	8857	26794;26795;26796	chr2:178607213;178607212;178607211	chr2:179471940;179471939;179471938
Novex-2	8924	26995;26996;26997	chr2:178607213;178607212;178607211	chr2:179471940;179471939;179471938
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: Fn3-17
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.5604
• 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	rs727503610	-0.036	0.059	N	0.292	0.154	0.294561560033	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
T/I	rs727503610	-0.036	0.059	N	0.292	0.154	0.294561560033	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
T/I	rs727503610	-0.036	0.059	N	0.292	0.154	0.294561560033	gnomAD-4.0.0	4.34004E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.08763E-06	0	1.6022E-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	0.1642	likely_benign	0.1588	benign	-0.71	Destabilizing	0.896	D	0.469	neutral	N	0.508403896	None	None	I
T/C	0.5165	ambiguous	0.5607	ambiguous	-0.464	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	I
T/D	0.6807	likely_pathogenic	0.5885	pathogenic	-0.132	Destabilizing	0.996	D	0.626	neutral	None	None	None	None	I
T/E	0.5611	ambiguous	0.4716	ambiguous	-0.164	Destabilizing	0.996	D	0.604	neutral	None	None	None	None	I
T/F	0.4879	ambiguous	0.4427	ambiguous	-0.884	Destabilizing	0.076	N	0.347	neutral	None	None	None	None	I
T/G	0.4405	ambiguous	0.4322	ambiguous	-0.927	Destabilizing	0.996	D	0.559	neutral	None	None	None	None	I
T/H	0.4822	ambiguous	0.4532	ambiguous	-1.221	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
T/I	0.257	likely_benign	0.2145	benign	-0.237	Destabilizing	0.059	N	0.292	neutral	N	0.500282617	None	None	I
T/K	0.4761	ambiguous	0.3602	ambiguous	-0.684	Destabilizing	0.984	D	0.623	neutral	N	0.470042566	None	None	I
T/L	0.1523	likely_benign	0.1503	benign	-0.237	Destabilizing	0.702	D	0.532	neutral	None	None	None	None	I
T/M	0.1258	likely_benign	0.1257	benign	0.072	Stabilizing	0.976	D	0.639	neutral	None	None	None	None	I
T/N	0.2515	likely_benign	0.2282	benign	-0.535	Destabilizing	0.996	D	0.559	neutral	None	None	None	None	I
T/P	0.6511	likely_pathogenic	0.5708	pathogenic	-0.363	Destabilizing	0.995	D	0.638	neutral	N	0.521534628	None	None	I
T/Q	0.4034	ambiguous	0.3697	ambiguous	-0.773	Destabilizing	0.996	D	0.643	neutral	None	None	None	None	I
T/R	0.4503	ambiguous	0.341	ambiguous	-0.395	Destabilizing	0.995	D	0.633	neutral	N	0.488084369	None	None	I
T/S	0.172	likely_benign	0.1753	benign	-0.81	Destabilizing	0.946	D	0.483	neutral	N	0.520791175	None	None	I
T/V	0.1998	likely_benign	0.1956	benign	-0.363	Destabilizing	0.702	D	0.497	neutral	None	None	None	None	I
T/W	0.8124	likely_pathogenic	0.7684	pathogenic	-0.795	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
T/Y	0.576	likely_pathogenic	0.5391	ambiguous	-0.571	Destabilizing	0.952	D	0.693	prob.neutral	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.