TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35318	106177;106178;106179	chr2:178530663;178530662;178530661	chr2:179395390;179395389;179395388
N2AB	33677	101254;101255;101256	chr2:178530663;178530662;178530661	chr2:179395390;179395389;179395388
N2A	32750	98473;98474;98475	chr2:178530663;178530662;178530661	chr2:179395390;179395389;179395388
N2B	26253	78982;78983;78984	chr2:178530663;178530662;178530661	chr2:179395390;179395389;179395388
Novex-1	26378	79357;79358;79359	chr2:178530663;178530662;178530661	chr2:179395390;179395389;179395388
Novex-2	26445	79558;79559;79560	chr2:178530663;178530662;178530661	chr2:179395390;179395389;179395388
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-165
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2061
• 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/N	rs1391706140	None	0.029	N	0.459	0.095	0.229924730088	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs1391706140	None	0.029	N	0.459	0.095	0.229924730088	gnomAD-4.0.0	6.57505E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	0	0
T/S	rs1688710616	None	None	N	0.183	0.162	0.143124449307	gnomAD-4.0.0	3.18173E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.715E-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
T/A	0.0802	likely_benign	0.0808	benign	-0.916	Destabilizing	None	N	0.133	neutral	N	0.49492523	None	None	N
T/C	0.3974	ambiguous	0.3915	ambiguous	-0.595	Destabilizing	0.356	N	0.527	neutral	None	None	None	None	N
T/D	0.3849	ambiguous	0.3867	ambiguous	-1.0	Destabilizing	0.072	N	0.484	neutral	None	None	None	None	N
T/E	0.349	ambiguous	0.3551	ambiguous	-0.86	Destabilizing	0.038	N	0.478	neutral	None	None	None	None	N
T/F	0.225	likely_benign	0.2341	benign	-0.531	Destabilizing	0.214	N	0.571	neutral	None	None	None	None	N
T/G	0.3044	likely_benign	0.3026	benign	-1.302	Destabilizing	0.016	N	0.46	neutral	None	None	None	None	N
T/H	0.2853	likely_benign	0.2851	benign	-1.46	Destabilizing	0.356	N	0.534	neutral	None	None	None	None	N
T/I	0.133	likely_benign	0.1311	benign	0.073	Stabilizing	0.012	N	0.431	neutral	D	0.525941571	None	None	N
T/K	0.2538	likely_benign	0.2505	benign	-0.821	Destabilizing	0.038	N	0.48	neutral	None	None	None	None	N
T/L	0.1154	likely_benign	0.1159	benign	0.073	Stabilizing	None	N	0.244	neutral	None	None	None	None	N
T/M	0.1084	likely_benign	0.1132	benign	0.117	Stabilizing	0.214	N	0.533	neutral	None	None	None	None	N
T/N	0.1374	likely_benign	0.1322	benign	-1.222	Destabilizing	0.029	N	0.459	neutral	N	0.511510836	None	None	N
T/P	0.524	ambiguous	0.5153	ambiguous	-0.224	Destabilizing	0.055	N	0.522	neutral	D	0.524943167	None	None	N
T/Q	0.2734	likely_benign	0.2777	benign	-1.068	Destabilizing	0.214	N	0.551	neutral	None	None	None	None	N
T/R	0.1924	likely_benign	0.1931	benign	-0.873	Destabilizing	0.072	N	0.544	neutral	None	None	None	None	N
T/S	0.1142	likely_benign	0.1139	benign	-1.431	Destabilizing	None	N	0.183	neutral	N	0.475027174	None	None	N
T/V	0.1285	likely_benign	0.1312	benign	-0.224	Destabilizing	None	N	0.136	neutral	None	None	None	None	N
T/W	0.6401	likely_pathogenic	0.651	pathogenic	-0.679	Destabilizing	0.864	D	0.553	neutral	None	None	None	None	N
T/Y	0.325	likely_benign	0.318	benign	-0.361	Destabilizing	0.356	N	0.568	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.