TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5911	17956;17957;17958	chr2:178730934;178730933;178730932	chr2:179595661;179595660;179595659
N2AB	5594	17005;17006;17007	chr2:178730934;178730933;178730932	chr2:179595661;179595660;179595659
N2A	4667	14224;14225;14226	chr2:178730934;178730933;178730932	chr2:179595661;179595660;179595659
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-42
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.4108
• Predicted PPI site: N

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/H	rs781725187	-0.731	0.989	N	0.423	0.364	0.292787519742	gnomAD-2.1.1	4.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.14E-06	0
N/H	rs781725187	-0.731	0.989	N	0.423	0.364	0.292787519742	gnomAD-4.0.0	1.62191E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91346E-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	0.1891	likely_benign	0.1991	benign	-1.007	Destabilizing	0.525	D	0.494	neutral	None	None	None	None	N
N/C	0.3287	likely_benign	0.3478	ambiguous	-0.154	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	N
N/D	0.1315	likely_benign	0.1319	benign	-0.506	Destabilizing	0.012	N	0.093	neutral	N	0.450326304	None	None	N
N/E	0.3435	ambiguous	0.347	ambiguous	-0.43	Destabilizing	0.525	D	0.351	neutral	None	None	None	None	N
N/F	0.5073	ambiguous	0.534	ambiguous	-0.838	Destabilizing	0.991	D	0.542	neutral	None	None	None	None	N
N/G	0.2939	likely_benign	0.3102	benign	-1.318	Destabilizing	0.525	D	0.355	neutral	None	None	None	None	N
N/H	0.0863	likely_benign	0.0887	benign	-0.989	Destabilizing	0.989	D	0.423	neutral	N	0.471144294	None	None	N
N/I	0.2384	likely_benign	0.2595	benign	-0.225	Destabilizing	0.934	D	0.509	neutral	N	0.47483796	None	None	N
N/K	0.2825	likely_benign	0.2859	benign	-0.233	Destabilizing	0.801	D	0.331	neutral	N	0.444570981	None	None	N
N/L	0.2706	likely_benign	0.2894	benign	-0.225	Destabilizing	0.842	D	0.501	neutral	None	None	None	None	N
N/M	0.3384	likely_benign	0.3537	ambiguous	0.284	Stabilizing	0.998	D	0.481	neutral	None	None	None	None	N
N/P	0.8994	likely_pathogenic	0.9165	pathogenic	-0.457	Destabilizing	0.974	D	0.467	neutral	None	None	None	None	N
N/Q	0.2968	likely_benign	0.3011	benign	-0.928	Destabilizing	0.974	D	0.377	neutral	None	None	None	None	N
N/R	0.2708	likely_benign	0.2658	benign	-0.158	Destabilizing	0.949	D	0.369	neutral	None	None	None	None	N
N/S	0.07	likely_benign	0.076	benign	-0.902	Destabilizing	0.051	N	0.097	neutral	N	0.444611053	None	None	N
N/T	0.0963	likely_benign	0.104	benign	-0.636	Destabilizing	0.022	N	0.077	neutral	N	0.371574732	None	None	N
N/V	0.2427	likely_benign	0.2568	benign	-0.457	Destabilizing	0.842	D	0.514	neutral	None	None	None	None	N
N/W	0.7571	likely_pathogenic	0.7604	pathogenic	-0.533	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
N/Y	0.1912	likely_benign	0.1957	benign	-0.352	Destabilizing	0.989	D	0.503	neutral	N	0.505160867	None	None	N

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.