TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21389	64390;64391;64392	chr2:178586736;178586735;178586734	chr2:179451463;179451462;179451461
N2AB	19748	59467;59468;59469	chr2:178586736;178586735;178586734	chr2:179451463;179451462;179451461
N2A	18821	56686;56687;56688	chr2:178586736;178586735;178586734	chr2:179451463;179451462;179451461
N2B	12324	37195;37196;37197	chr2:178586736;178586735;178586734	chr2:179451463;179451462;179451461
Novex-1	12449	37570;37571;37572	chr2:178586736;178586735;178586734	chr2:179451463;179451462;179451461
Novex-2	12516	37771;37772;37773	chr2:178586736;178586735;178586734	chr2:179451463;179451462;179451461
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-43
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.3923
• 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/T	rs2049063426	None	0.989	D	0.617	0.341	0.537402380065	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/T	rs2049063426	None	0.989	D	0.617	0.341	0.537402380065	gnomAD-4.0.0	6.57756E-06	None	None	None	None	I	None	2.41406E-05	0	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
P/A	0.1473	likely_benign	0.1303	benign	-1.881	Destabilizing	0.978	D	0.51	neutral	N	0.470826502	None	None	I
P/C	0.8072	likely_pathogenic	0.7716	pathogenic	-1.208	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/D	0.9476	likely_pathogenic	0.9016	pathogenic	-2.299	Highly Destabilizing	0.998	D	0.639	neutral	None	None	None	None	I
P/E	0.7006	likely_pathogenic	0.5651	pathogenic	-2.14	Highly Destabilizing	0.983	D	0.547	neutral	None	None	None	None	I
P/F	0.8554	likely_pathogenic	0.8298	pathogenic	-1.269	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
P/G	0.746	likely_pathogenic	0.679	pathogenic	-2.329	Highly Destabilizing	0.992	D	0.637	neutral	None	None	None	None	I
P/H	0.5383	ambiguous	0.4489	ambiguous	-1.835	Destabilizing	1.0	D	0.755	deleterious	N	0.477340856	None	None	I
P/I	0.5829	likely_pathogenic	0.551	ambiguous	-0.666	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	I
P/K	0.4316	ambiguous	0.3498	ambiguous	-1.619	Destabilizing	0.246	N	0.305	neutral	None	None	None	None	I
P/L	0.2572	likely_benign	0.2312	benign	-0.666	Destabilizing	0.997	D	0.713	prob.delet.	N	0.482594321	None	None	I
P/M	0.5535	ambiguous	0.5124	ambiguous	-0.522	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/N	0.8383	likely_pathogenic	0.7811	pathogenic	-1.799	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	I
P/Q	0.3425	ambiguous	0.2716	benign	-1.767	Destabilizing	0.995	D	0.69	prob.neutral	None	None	None	None	I
P/R	0.384	ambiguous	0.3073	benign	-1.264	Destabilizing	0.987	D	0.663	neutral	N	0.495706303	None	None	I
P/S	0.4283	ambiguous	0.3533	ambiguous	-2.345	Highly Destabilizing	0.978	D	0.592	neutral	N	0.507654093	None	None	I
P/T	0.3472	ambiguous	0.2922	benign	-2.052	Highly Destabilizing	0.989	D	0.617	neutral	D	0.522911547	None	None	I
P/V	0.3882	ambiguous	0.3719	ambiguous	-1.043	Destabilizing	0.998	D	0.659	neutral	None	None	None	None	I
P/W	0.9404	likely_pathogenic	0.9143	pathogenic	-1.658	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/Y	0.8204	likely_pathogenic	0.7652	pathogenic	-1.274	Destabilizing	0.999	D	0.812	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.