TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16933	51022;51023;51024	chr2:178611432;178611431;178611430	chr2:179476159;179476158;179476157
N2AB	15292	46099;46100;46101	chr2:178611432;178611431;178611430	chr2:179476159;179476158;179476157
N2A	14365	43318;43319;43320	chr2:178611432;178611431;178611430	chr2:179476159;179476158;179476157
N2B	7868	23827;23828;23829	chr2:178611432;178611431;178611430	chr2:179476159;179476158;179476157
Novex-1	7993	24202;24203;24204	chr2:178611432;178611431;178611430	chr2:179476159;179476158;179476157
Novex-2	8060	24403;24404;24405	chr2:178611432;178611431;178611430	chr2:179476159;179476158;179476157
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-11
• Domain position: 82
• Structural Position: 113
• Q(SASA): 0.5248
• 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
A/T	rs794729452	-0.402	0.925	N	0.377	0.19	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
A/T	rs794729452	-0.402	0.925	N	0.377	0.19	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs794729452	-0.402	0.925	N	0.377	0.19	None	gnomAD-4.0.0	9.92066E-06	None	None	None	None	I	None	6.67878E-05	0	None	0	0	None	0	0	9.32754E-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
A/C	0.4922	ambiguous	0.6558	pathogenic	-0.866	Destabilizing	1.0	D	0.357	neutral	None	None	None	None	I
A/D	0.4601	ambiguous	0.5499	ambiguous	-0.416	Destabilizing	0.989	D	0.521	neutral	N	0.445703351	None	None	I
A/E	0.4034	ambiguous	0.4978	ambiguous	-0.559	Destabilizing	0.97	D	0.433	neutral	None	None	None	None	I
A/F	0.5061	ambiguous	0.6585	pathogenic	-0.814	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
A/G	0.1417	likely_benign	0.1822	benign	-0.327	Destabilizing	0.91	D	0.381	neutral	N	0.469898004	None	None	I
A/H	0.5486	ambiguous	0.6452	pathogenic	-0.272	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	I
A/I	0.2914	likely_benign	0.435	ambiguous	-0.331	Destabilizing	0.996	D	0.457	neutral	None	None	None	None	I
A/K	0.5916	likely_pathogenic	0.7013	pathogenic	-0.667	Destabilizing	0.304	N	0.339	neutral	None	None	None	None	I
A/L	0.2343	likely_benign	0.3247	benign	-0.331	Destabilizing	0.985	D	0.433	neutral	None	None	None	None	I
A/M	0.2849	likely_benign	0.3936	ambiguous	-0.479	Destabilizing	1.0	D	0.454	neutral	None	None	None	None	I
A/N	0.2678	likely_benign	0.3353	benign	-0.406	Destabilizing	0.991	D	0.515	neutral	None	None	None	None	I
A/P	0.3489	ambiguous	0.4012	ambiguous	-0.28	Destabilizing	0.994	D	0.443	neutral	N	0.48155311	None	None	I
A/Q	0.4014	ambiguous	0.4724	ambiguous	-0.656	Destabilizing	0.991	D	0.459	neutral	None	None	None	None	I
A/R	0.566	likely_pathogenic	0.6516	pathogenic	-0.2	Destabilizing	0.983	D	0.403	neutral	None	None	None	None	I
A/S	0.098	likely_benign	0.0981	benign	-0.625	Destabilizing	0.287	N	0.126	neutral	N	0.416670317	None	None	I
A/T	0.0964	likely_benign	0.1155	benign	-0.683	Destabilizing	0.925	D	0.377	neutral	N	0.477707631	None	None	I
A/V	0.1532	likely_benign	0.2228	benign	-0.28	Destabilizing	0.98	D	0.373	neutral	N	0.482403351	None	None	I
A/W	0.8657	likely_pathogenic	0.9328	pathogenic	-0.951	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
A/Y	0.6116	likely_pathogenic	0.756	pathogenic	-0.615	Destabilizing	0.999	D	0.613	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.