TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23869	71830;71831;71832	chr2:178574527;178574526;178574525	chr2:179439254;179439253;179439252
N2AB	22228	66907;66908;66909	chr2:178574527;178574526;178574525	chr2:179439254;179439253;179439252
N2A	21301	64126;64127;64128	chr2:178574527;178574526;178574525	chr2:179439254;179439253;179439252
N2B	14804	44635;44636;44637	chr2:178574527;178574526;178574525	chr2:179439254;179439253;179439252
Novex-1	14929	45010;45011;45012	chr2:178574527;178574526;178574525	chr2:179439254;179439253;179439252
Novex-2	14996	45211;45212;45213	chr2:178574527;178574526;178574525	chr2:179439254;179439253;179439252
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-61
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.8238
• 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
N/K	rs1709390965	None	0.942	N	0.46	0.292	0.165133752707	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
N/K	rs1709390965	None	0.942	N	0.46	0.292	0.165133752707	gnomAD-4.0.0	3.09901E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.23865E-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
N/A	0.4439	ambiguous	0.4589	ambiguous	-0.12	Destabilizing	0.86	D	0.426	neutral	None	None	None	None	I
N/C	0.4629	ambiguous	0.4796	ambiguous	0.124	Stabilizing	0.998	D	0.639	neutral	None	None	None	None	I
N/D	0.4161	ambiguous	0.4276	ambiguous	-0.018	Destabilizing	0.966	D	0.48	neutral	N	0.49822096	None	None	I
N/E	0.7461	likely_pathogenic	0.7701	pathogenic	-0.086	Destabilizing	0.926	D	0.458	neutral	None	None	None	None	I
N/F	0.7594	likely_pathogenic	0.7692	pathogenic	-0.726	Destabilizing	0.915	D	0.61	neutral	None	None	None	None	I
N/G	0.3667	ambiguous	0.3713	ambiguous	-0.204	Destabilizing	0.926	D	0.453	neutral	None	None	None	None	I
N/H	0.2182	likely_benign	0.226	benign	-0.213	Destabilizing	0.942	D	0.512	neutral	N	0.484401066	None	None	I
N/I	0.5805	likely_pathogenic	0.5711	pathogenic	None	Stabilizing	0.942	D	0.601	neutral	N	0.493048346	None	None	I
N/K	0.6844	likely_pathogenic	0.6948	pathogenic	0.068	Stabilizing	0.942	D	0.46	neutral	N	0.500935978	None	None	I
N/L	0.4333	ambiguous	0.4497	ambiguous	None	Stabilizing	0.915	D	0.526	neutral	None	None	None	None	I
N/M	0.5496	ambiguous	0.5602	ambiguous	0.091	Stabilizing	0.998	D	0.537	neutral	None	None	None	None	I
N/P	0.7981	likely_pathogenic	0.7953	pathogenic	-0.018	Destabilizing	0.993	D	0.543	neutral	None	None	None	None	I
N/Q	0.6023	likely_pathogenic	0.6302	pathogenic	-0.316	Destabilizing	0.978	D	0.495	neutral	None	None	None	None	I
N/R	0.6765	likely_pathogenic	0.6932	pathogenic	0.158	Stabilizing	0.978	D	0.516	neutral	None	None	None	None	I
N/S	0.1162	likely_benign	0.1166	benign	-0.066	Destabilizing	0.822	D	0.471	neutral	N	0.458126563	None	None	I
N/T	0.2329	likely_benign	0.2388	benign	-0.028	Destabilizing	0.904	D	0.455	neutral	N	0.519791098	None	None	I
N/V	0.5624	ambiguous	0.5637	ambiguous	-0.018	Destabilizing	0.956	D	0.602	neutral	None	None	None	None	I
N/W	0.8832	likely_pathogenic	0.889	pathogenic	-0.858	Destabilizing	0.994	D	0.622	neutral	None	None	None	None	I
N/Y	0.31	likely_benign	0.3225	benign	-0.538	Destabilizing	0.032	N	0.404	neutral	N	0.496010861	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.