TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6225	18898;18899;18900	chr2:178729483;178729482;178729481	chr2:179594210;179594209;179594208
N2AB	5908	17947;17948;17949	chr2:178729483;178729482;178729481	chr2:179594210;179594209;179594208
N2A	4981	15166;15167;15168	chr2:178729483;178729482;178729481	chr2:179594210;179594209;179594208
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-46
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5662
• 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/A	rs794727818	None	0.948	D	0.528	0.224	0.32471235697	gnomAD-4.0.0	1.36859E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.31356E-05
T/K	None	None	0.997	N	0.612	0.363	0.589254406313	gnomAD-4.0.0	1.59172E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41663E-04	0	0	0
T/S	None	None	0.775	N	0.28	0.127	0.234412748748	gnomAD-4.0.0	6.84296E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99575E-07	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	0.2609	likely_benign	0.2835	benign	-0.405	Destabilizing	0.948	D	0.528	neutral	D	0.528440371	None	None	I
T/C	0.8122	likely_pathogenic	0.8508	pathogenic	-0.423	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
T/D	0.6334	likely_pathogenic	0.662	pathogenic	0.148	Stabilizing	0.998	D	0.607	neutral	None	None	None	None	I
T/E	0.5873	likely_pathogenic	0.6229	pathogenic	0.106	Stabilizing	0.998	D	0.614	neutral	None	None	None	None	I
T/F	0.4423	ambiguous	0.5331	ambiguous	-0.817	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
T/G	0.5769	likely_pathogenic	0.5838	pathogenic	-0.564	Destabilizing	0.992	D	0.645	neutral	None	None	None	None	I
T/H	0.4962	ambiguous	0.5811	pathogenic	-0.69	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
T/I	0.4104	ambiguous	0.5351	ambiguous	-0.097	Destabilizing	0.998	D	0.671	neutral	N	0.504776865	None	None	I
T/K	0.4916	ambiguous	0.5687	pathogenic	-0.409	Destabilizing	0.997	D	0.612	neutral	N	0.500619052	None	None	I
T/L	0.226	likely_benign	0.2843	benign	-0.097	Destabilizing	0.996	D	0.645	neutral	None	None	None	None	I
T/M	0.156	likely_benign	0.1836	benign	-0.205	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
T/N	0.2465	likely_benign	0.2907	benign	-0.298	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	I
T/P	0.4028	ambiguous	0.5097	ambiguous	-0.17	Destabilizing	0.998	D	0.67	neutral	N	0.494317291	None	None	I
T/Q	0.4743	ambiguous	0.5367	ambiguous	-0.431	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
T/R	0.4426	ambiguous	0.5235	ambiguous	-0.125	Destabilizing	0.998	D	0.663	neutral	D	0.523477269	None	None	I
T/S	0.1777	likely_benign	0.1839	benign	-0.504	Destabilizing	0.775	D	0.28	neutral	N	0.454732046	None	None	I
T/V	0.365	ambiguous	0.4742	ambiguous	-0.17	Destabilizing	0.996	D	0.631	neutral	None	None	None	None	I
T/W	0.7647	likely_pathogenic	0.8035	pathogenic	-0.866	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
T/Y	0.504	ambiguous	0.5672	pathogenic	-0.566	Destabilizing	1.0	D	0.709	prob.delet.	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.