TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27602	83029;83030;83031	chr2:178563328;178563327;178563326	chr2:179428055;179428054;179428053
N2AB	25961	78106;78107;78108	chr2:178563328;178563327;178563326	chr2:179428055;179428054;179428053
N2A	25034	75325;75326;75327	chr2:178563328;178563327;178563326	chr2:179428055;179428054;179428053
N2B	18537	55834;55835;55836	chr2:178563328;178563327;178563326	chr2:179428055;179428054;179428053
Novex-1	18662	56209;56210;56211	chr2:178563328;178563327;178563326	chr2:179428055;179428054;179428053
Novex-2	18729	56410;56411;56412	chr2:178563328;178563327;178563326	chr2:179428055;179428054;179428053
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-89
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.3623
• 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
V/L	rs886038821	None	None	N	0.245	0.094	0.226586394389	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs886038821	None	None	N	0.245	0.094	0.226586394389	gnomAD-4.0.0	5.12538E-06	None	None	None	None	I	None	5.07477E-05	0	None	0	0	None	0	0	2.39331E-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	0.8217	likely_pathogenic	0.769	pathogenic	-1.915	Destabilizing	0.104	N	0.635	neutral	N	0.512787767	None	None	I
V/C	0.9246	likely_pathogenic	0.9149	pathogenic	-1.119	Destabilizing	0.968	D	0.754	deleterious	None	None	None	None	I
V/D	0.9861	likely_pathogenic	0.9779	pathogenic	-2.156	Highly Destabilizing	0.667	D	0.83	deleterious	N	0.496106161	None	None	I
V/E	0.9503	likely_pathogenic	0.9253	pathogenic	-2.085	Highly Destabilizing	0.726	D	0.803	deleterious	None	None	None	None	I
V/F	0.7204	likely_pathogenic	0.661	pathogenic	-1.329	Destabilizing	0.497	N	0.775	deleterious	N	0.481839717	None	None	I
V/G	0.8797	likely_pathogenic	0.8348	pathogenic	-2.311	Highly Destabilizing	0.667	D	0.82	deleterious	N	0.496237897	None	None	I
V/H	0.9858	likely_pathogenic	0.9811	pathogenic	-1.974	Destabilizing	0.968	D	0.816	deleterious	None	None	None	None	I
V/I	0.0676	likely_benign	0.0742	benign	-0.876	Destabilizing	None	N	0.187	neutral	N	0.353473682	None	None	I
V/K	0.9703	likely_pathogenic	0.9563	pathogenic	-1.709	Destabilizing	0.726	D	0.802	deleterious	None	None	None	None	I
V/L	0.3032	likely_benign	0.2744	benign	-0.876	Destabilizing	None	N	0.245	neutral	N	0.477749687	None	None	I
V/M	0.4377	ambiguous	0.3909	ambiguous	-0.56	Destabilizing	0.567	D	0.669	neutral	None	None	None	None	I
V/N	0.9435	likely_pathogenic	0.9245	pathogenic	-1.568	Destabilizing	0.89	D	0.837	deleterious	None	None	None	None	I
V/P	0.8663	likely_pathogenic	0.8551	pathogenic	-1.192	Destabilizing	0.89	D	0.803	deleterious	None	None	None	None	I
V/Q	0.9508	likely_pathogenic	0.9298	pathogenic	-1.654	Destabilizing	0.89	D	0.811	deleterious	None	None	None	None	I
V/R	0.9554	likely_pathogenic	0.9358	pathogenic	-1.219	Destabilizing	0.726	D	0.835	deleterious	None	None	None	None	I
V/S	0.9064	likely_pathogenic	0.866	pathogenic	-2.079	Highly Destabilizing	0.726	D	0.799	deleterious	None	None	None	None	I
V/T	0.8154	likely_pathogenic	0.7698	pathogenic	-1.902	Destabilizing	0.272	N	0.668	neutral	None	None	None	None	I
V/W	0.9865	likely_pathogenic	0.9828	pathogenic	-1.684	Destabilizing	0.968	D	0.803	deleterious	None	None	None	None	I
V/Y	0.9616	likely_pathogenic	0.9431	pathogenic	-1.395	Destabilizing	0.726	D	0.771	deleterious	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.