TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28173	84742;84743;84744	chr2:178561615;178561614;178561613	chr2:179426342;179426341;179426340
N2AB	26532	79819;79820;79821	chr2:178561615;178561614;178561613	chr2:179426342;179426341;179426340
N2A	25605	77038;77039;77040	chr2:178561615;178561614;178561613	chr2:179426342;179426341;179426340
N2B	19108	57547;57548;57549	chr2:178561615;178561614;178561613	chr2:179426342;179426341;179426340
Novex-1	19233	57922;57923;57924	chr2:178561615;178561614;178561613	chr2:179426342;179426341;179426340
Novex-2	19300	58123;58124;58125	chr2:178561615;178561614;178561613	chr2:179426342;179426341;179426340
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-93
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1128
• 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
V/A	rs1559299770	None	0.999	N	0.636	0.503	0.623315389809	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
V/I	rs1703687594	None	0.997	N	0.543	0.308	0.442363741745	gnomAD-4.0.0	1.36935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79965E-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
V/A	0.8391	likely_pathogenic	0.8272	pathogenic	-2.268	Highly Destabilizing	0.999	D	0.636	neutral	N	0.497808059	None	None	N
V/C	0.9558	likely_pathogenic	0.9513	pathogenic	-1.636	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9974	pathogenic	-3.394	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/E	0.9929	likely_pathogenic	0.9912	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.873	deleterious	N	0.521534628	None	None	N
V/F	0.8474	likely_pathogenic	0.8248	pathogenic	-1.38	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/G	0.9337	likely_pathogenic	0.9305	pathogenic	-2.836	Highly Destabilizing	1.0	D	0.878	deleterious	N	0.521534628	None	None	N
V/H	0.9971	likely_pathogenic	0.9965	pathogenic	-2.837	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/I	0.0931	likely_benign	0.0904	benign	-0.615	Destabilizing	0.997	D	0.543	neutral	N	0.453910035	None	None	N
V/K	0.9941	likely_pathogenic	0.9931	pathogenic	-1.99	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/L	0.3654	ambiguous	0.3285	benign	-0.615	Destabilizing	0.997	D	0.652	neutral	N	0.41947967	None	None	N
V/M	0.6206	likely_pathogenic	0.5924	pathogenic	-0.761	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
V/N	0.9929	likely_pathogenic	0.991	pathogenic	-2.64	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/P	0.9891	likely_pathogenic	0.9881	pathogenic	-1.149	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/Q	0.9901	likely_pathogenic	0.9883	pathogenic	-2.314	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/R	0.9894	likely_pathogenic	0.9874	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/S	0.9729	likely_pathogenic	0.9693	pathogenic	-3.087	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/T	0.9159	likely_pathogenic	0.9038	pathogenic	-2.643	Highly Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
V/W	0.9982	likely_pathogenic	0.9977	pathogenic	-2.027	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Y	0.99	likely_pathogenic	0.9882	pathogenic	-1.663	Destabilizing	1.0	D	0.761	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.