TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17264	52015;52016;52017	chr2:178609520;178609519;178609518	chr2:179474247;179474246;179474245
N2AB	15623	47092;47093;47094	chr2:178609520;178609519;178609518	chr2:179474247;179474246;179474245
N2A	14696	44311;44312;44313	chr2:178609520;178609519;178609518	chr2:179474247;179474246;179474245
N2B	8199	24820;24821;24822	chr2:178609520;178609519;178609518	chr2:179474247;179474246;179474245
Novex-1	8324	25195;25196;25197	chr2:178609520;178609519;178609518	chr2:179474247;179474246;179474245
Novex-2	8391	25396;25397;25398	chr2:178609520;178609519;178609518	chr2:179474247;179474246;179474245
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-112
• Domain position: 14
• Structural Position: 26
• Q(SASA): 0.398
• 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
E/K	rs566710566	-0.082	0.565	N	0.489	0.149	0.180583059064	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/K	rs566710566	-0.082	0.565	N	0.489	0.149	0.180583059064	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
E/K	rs566710566	-0.082	0.565	N	0.489	0.149	0.180583059064	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/K	rs566710566	-0.082	0.565	N	0.489	0.149	0.180583059064	gnomAD-4.0.0	6.57652E-06	None	None	None	None	N	None	0	6.55996E-05	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
E/A	0.3127	likely_benign	0.2734	benign	-0.847	Destabilizing	0.008	N	0.282	neutral	N	0.481528206	None	None	N
E/C	0.9133	likely_pathogenic	0.8968	pathogenic	-0.366	Destabilizing	0.989	D	0.719	prob.delet.	None	None	None	None	N
E/D	0.24	likely_benign	0.2346	benign	-0.85	Destabilizing	0.008	N	0.187	neutral	N	0.462998373	None	None	N
E/F	0.8871	likely_pathogenic	0.8558	pathogenic	-0.442	Destabilizing	0.961	D	0.69	prob.neutral	None	None	None	None	N
E/G	0.4906	ambiguous	0.4193	ambiguous	-1.162	Destabilizing	0.565	D	0.548	neutral	N	0.467288682	None	None	N
E/H	0.7596	likely_pathogenic	0.7112	pathogenic	-0.604	Destabilizing	0.923	D	0.509	neutral	None	None	None	None	N
E/I	0.5151	ambiguous	0.4879	ambiguous	-0.003	Destabilizing	0.923	D	0.688	prob.neutral	None	None	None	None	N
E/K	0.4167	ambiguous	0.3486	ambiguous	-0.287	Destabilizing	0.565	D	0.489	neutral	N	0.449666504	None	None	N
E/L	0.6433	likely_pathogenic	0.5958	pathogenic	-0.003	Destabilizing	0.858	D	0.579	neutral	None	None	None	None	N
E/M	0.6235	likely_pathogenic	0.6007	pathogenic	0.357	Stabilizing	0.996	D	0.655	neutral	None	None	None	None	N
E/N	0.5003	ambiguous	0.4653	ambiguous	-0.74	Destabilizing	0.024	N	0.263	neutral	None	None	None	None	N
E/P	0.7523	likely_pathogenic	0.6849	pathogenic	-0.264	Destabilizing	0.961	D	0.577	neutral	None	None	None	None	N
E/Q	0.3208	likely_benign	0.2844	benign	-0.651	Destabilizing	0.901	D	0.503	neutral	N	0.489051611	None	None	N
E/R	0.5969	likely_pathogenic	0.5206	ambiguous	-0.058	Destabilizing	0.923	D	0.493	neutral	None	None	None	None	N
E/S	0.4047	ambiguous	0.3641	ambiguous	-1.0	Destabilizing	0.633	D	0.474	neutral	None	None	None	None	N
E/T	0.3583	ambiguous	0.3248	benign	-0.738	Destabilizing	0.775	D	0.514	neutral	None	None	None	None	N
E/V	0.331	likely_benign	0.3064	benign	-0.264	Destabilizing	0.82	D	0.557	neutral	N	0.481874923	None	None	N
E/W	0.9681	likely_pathogenic	0.9555	pathogenic	-0.182	Destabilizing	0.996	D	0.736	prob.delet.	None	None	None	None	N
E/Y	0.8276	likely_pathogenic	0.7835	pathogenic	-0.179	Destabilizing	0.987	D	0.662	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.