TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16882	50869;50870;50871	chr2:178611585;178611584;178611583	chr2:179476312;179476311;179476310
N2AB	15241	45946;45947;45948	chr2:178611585;178611584;178611583	chr2:179476312;179476311;179476310
N2A	14314	43165;43166;43167	chr2:178611585;178611584;178611583	chr2:179476312;179476311;179476310
N2B	7817	23674;23675;23676	chr2:178611585;178611584;178611583	chr2:179476312;179476311;179476310
Novex-1	7942	24049;24050;24051	chr2:178611585;178611584;178611583	chr2:179476312;179476311;179476310
Novex-2	8009	24250;24251;24252	chr2:178611585;178611584;178611583	chr2:179476312;179476311;179476310
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-11
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2689
• 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
S/R	None	None	0.997	D	0.645	0.393	0.352048277211	gnomAD-4.0.0	1.59287E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86128E-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
S/A	0.2274	likely_benign	0.1883	benign	-0.54	Destabilizing	0.964	D	0.581	neutral	None	None	None	None	I
S/C	0.1732	likely_benign	0.1675	benign	-0.365	Destabilizing	0.135	N	0.467	neutral	N	0.486435574	None	None	I
S/D	0.9559	likely_pathogenic	0.9523	pathogenic	-0.162	Destabilizing	0.993	D	0.669	neutral	None	None	None	None	I
S/E	0.9485	likely_pathogenic	0.9553	pathogenic	-0.217	Destabilizing	0.993	D	0.668	neutral	None	None	None	None	I
S/F	0.5793	likely_pathogenic	0.6126	pathogenic	-0.922	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I
S/G	0.3885	ambiguous	0.2637	benign	-0.724	Destabilizing	0.99	D	0.62	neutral	N	0.472026425	None	None	I
S/H	0.7612	likely_pathogenic	0.7922	pathogenic	-1.277	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	I
S/I	0.6478	likely_pathogenic	0.6442	pathogenic	-0.175	Destabilizing	0.994	D	0.701	prob.neutral	D	0.602591385	None	None	I
S/K	0.9766	likely_pathogenic	0.9816	pathogenic	-0.644	Destabilizing	0.993	D	0.667	neutral	None	None	None	None	I
S/L	0.2712	likely_benign	0.3007	benign	-0.175	Destabilizing	0.985	D	0.654	neutral	None	None	None	None	I
S/M	0.4767	ambiguous	0.4987	ambiguous	0.195	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	I
S/N	0.5986	likely_pathogenic	0.6007	pathogenic	-0.459	Destabilizing	0.99	D	0.689	prob.neutral	D	0.530865476	None	None	I
S/P	0.9933	likely_pathogenic	0.9904	pathogenic	-0.265	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	I
S/Q	0.8726	likely_pathogenic	0.8867	pathogenic	-0.717	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
S/R	0.969	likely_pathogenic	0.9706	pathogenic	-0.456	Destabilizing	0.997	D	0.645	neutral	D	0.548217803	None	None	I
S/T	0.2777	likely_benign	0.2868	benign	-0.525	Destabilizing	0.4	N	0.438	neutral	N	0.480107017	None	None	I
S/V	0.5891	likely_pathogenic	0.5964	pathogenic	-0.265	Destabilizing	0.985	D	0.691	prob.neutral	None	None	None	None	I
S/W	0.8362	likely_pathogenic	0.8629	pathogenic	-0.886	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
S/Y	0.5636	ambiguous	0.6317	pathogenic	-0.626	Destabilizing	0.999	D	0.717	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.