TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8142	24649;24650;24651	chr2:178718776;178718775;178718774	chr2:179583503;179583502;179583501
N2AB	7825	23698;23699;23700	chr2:178718776;178718775;178718774	chr2:179583503;179583502;179583501
N2A	6898	20917;20918;20919	chr2:178718776;178718775;178718774	chr2:179583503;179583502;179583501
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-66
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.514
• 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
P/S	None	None	0.27	N	0.27	0.157	0.104622674875	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
P/T	rs990633841	None	0.023	N	0.215	0.177	0.156986980423	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs990633841	None	0.023	N	0.215	0.177	0.156986980423	gnomAD-4.0.0	3.04509E-06	None	None	None	None	I	None	3.49601E-05	0	None	0	0	None	0	0	0	0	3.40252E-05

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
P/A	0.0898	likely_benign	0.0876	benign	-1.135	Destabilizing	0.27	N	0.277	neutral	N	0.468252264	None	None	I
P/C	0.5894	likely_pathogenic	0.5148	ambiguous	-0.818	Destabilizing	0.995	D	0.299	neutral	None	None	None	None	I
P/D	0.451	ambiguous	0.4297	ambiguous	-0.928	Destabilizing	0.704	D	0.345	neutral	None	None	None	None	I
P/E	0.2883	likely_benign	0.2778	benign	-0.998	Destabilizing	0.704	D	0.267	neutral	None	None	None	None	I
P/F	0.4464	ambiguous	0.4367	ambiguous	-1.054	Destabilizing	0.893	D	0.385	neutral	None	None	None	None	I
P/G	0.3005	likely_benign	0.2969	benign	-1.364	Destabilizing	0.704	D	0.324	neutral	None	None	None	None	I
P/H	0.2167	likely_benign	0.2038	benign	-0.876	Destabilizing	0.981	D	0.284	neutral	None	None	None	None	I
P/I	0.2241	likely_benign	0.2253	benign	-0.644	Destabilizing	0.013	N	0.213	neutral	None	None	None	None	I
P/K	0.302	likely_benign	0.296	benign	-1.025	Destabilizing	0.031	N	0.236	neutral	None	None	None	None	I
P/L	0.1044	likely_benign	0.1019	benign	-0.644	Destabilizing	0.002	N	0.213	neutral	N	0.482565569	None	None	I
P/M	0.2859	likely_benign	0.2835	benign	-0.474	Destabilizing	0.893	D	0.304	neutral	None	None	None	None	I
P/N	0.3059	likely_benign	0.2917	benign	-0.737	Destabilizing	0.704	D	0.349	neutral	None	None	None	None	I
P/Q	0.1769	likely_benign	0.1704	benign	-0.984	Destabilizing	0.863	D	0.347	neutral	N	0.506463936	None	None	I
P/R	0.1949	likely_benign	0.1923	benign	-0.415	Destabilizing	0.006	N	0.213	neutral	N	0.465134601	None	None	I
P/S	0.1324	likely_benign	0.1263	benign	-1.168	Destabilizing	0.27	N	0.27	neutral	N	0.466521468	None	None	I
P/T	0.1082	likely_benign	0.1056	benign	-1.138	Destabilizing	0.023	N	0.215	neutral	N	0.446050195	None	None	I
P/V	0.166	likely_benign	0.1655	benign	-0.772	Destabilizing	0.013	N	0.195	neutral	None	None	None	None	I
P/W	0.6254	likely_pathogenic	0.6146	pathogenic	-1.154	Destabilizing	0.995	D	0.321	neutral	None	None	None	None	I
P/Y	0.4033	ambiguous	0.3903	ambiguous	-0.892	Destabilizing	0.981	D	0.347	neutral	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.