TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17757	53494;53495;53496	chr2:178607419;178607418;178607417	chr2:179472146;179472145;179472144
N2AB	16116	48571;48572;48573	chr2:178607419;178607418;178607417	chr2:179472146;179472145;179472144
N2A	15189	45790;45791;45792	chr2:178607419;178607418;178607417	chr2:179472146;179472145;179472144
N2B	8692	26299;26300;26301	chr2:178607419;178607418;178607417	chr2:179472146;179472145;179472144
Novex-1	8817	26674;26675;26676	chr2:178607419;178607418;178607417	chr2:179472146;179472145;179472144
Novex-2	8884	26875;26876;26877	chr2:178607419;178607418;178607417	chr2:179472146;179472145;179472144
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-113
• Domain position: 81
• Structural Position: 172
• Q(SASA): 0.1578
• 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
A/V	rs1351014934	None	None	N	0.141	0.109	0.193865811164	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	1.47E-05	0	0
A/V	rs1351014934	None	None	N	0.141	0.109	0.193865811164	gnomAD-4.0.0	3.72001E-06	None	None	None	None	N	None	1.33629E-05	0	None	0	0	None	0	0	4.23965E-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
A/C	0.4153	ambiguous	0.4108	ambiguous	-0.9	Destabilizing	0.001	N	0.372	neutral	None	None	None	None	N
A/D	0.9611	likely_pathogenic	0.9226	pathogenic	-1.076	Destabilizing	0.055	N	0.747	deleterious	D	0.526885859	None	None	N
A/E	0.9107	likely_pathogenic	0.8192	pathogenic	-1.002	Destabilizing	0.072	N	0.715	prob.delet.	None	None	None	None	N
A/F	0.674	likely_pathogenic	0.5618	ambiguous	-0.649	Destabilizing	0.214	N	0.773	deleterious	None	None	None	None	N
A/G	0.4082	ambiguous	0.3642	ambiguous	-1.171	Destabilizing	0.055	N	0.544	neutral	N	0.519634461	None	None	N
A/H	0.9296	likely_pathogenic	0.876	pathogenic	-1.42	Destabilizing	0.864	D	0.732	prob.delet.	None	None	None	None	N
A/I	0.2807	likely_benign	0.2222	benign	0.106	Stabilizing	0.006	N	0.623	neutral	None	None	None	None	N
A/K	0.9485	likely_pathogenic	0.8928	pathogenic	-1.098	Destabilizing	0.072	N	0.715	prob.delet.	None	None	None	None	N
A/L	0.3179	likely_benign	0.2426	benign	0.106	Stabilizing	0.016	N	0.599	neutral	None	None	None	None	N
A/M	0.3523	ambiguous	0.2848	benign	-0.062	Destabilizing	0.214	N	0.743	deleterious	None	None	None	None	N
A/N	0.8227	likely_pathogenic	0.738	pathogenic	-1.024	Destabilizing	0.214	N	0.776	deleterious	None	None	None	None	N
A/P	0.9337	likely_pathogenic	0.8771	pathogenic	-0.15	Destabilizing	0.295	N	0.766	deleterious	D	0.526885859	None	None	N
A/Q	0.8648	likely_pathogenic	0.7675	pathogenic	-0.993	Destabilizing	0.356	N	0.763	deleterious	None	None	None	None	N
A/R	0.9183	likely_pathogenic	0.844	pathogenic	-0.996	Destabilizing	0.214	N	0.77	deleterious	None	None	None	None	N
A/S	0.2137	likely_benign	0.1943	benign	-1.48	Destabilizing	0.012	N	0.519	neutral	D	0.536275995	None	None	N
A/T	0.0825	likely_benign	0.0825	benign	-1.278	Destabilizing	None	N	0.138	neutral	N	0.488695478	None	None	N
A/V	0.1268	likely_benign	0.1018	benign	-0.15	Destabilizing	None	N	0.141	neutral	N	0.423334491	None	None	N
A/W	0.9571	likely_pathogenic	0.9231	pathogenic	-1.165	Destabilizing	0.864	D	0.753	deleterious	None	None	None	None	N
A/Y	0.8824	likely_pathogenic	0.8186	pathogenic	-0.65	Destabilizing	0.356	N	0.769	deleterious	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.