TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23217	69874;69875;69876	chr2:178576595;178576594;178576593	chr2:179441322;179441321;179441320
N2AB	21576	64951;64952;64953	chr2:178576595;178576594;178576593	chr2:179441322;179441321;179441320
N2A	20649	62170;62171;62172	chr2:178576595;178576594;178576593	chr2:179441322;179441321;179441320
N2B	14152	42679;42680;42681	chr2:178576595;178576594;178576593	chr2:179441322;179441321;179441320
Novex-1	14277	43054;43055;43056	chr2:178576595;178576594;178576593	chr2:179441322;179441321;179441320
Novex-2	14344	43255;43256;43257	chr2:178576595;178576594;178576593	chr2:179441322;179441321;179441320
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-56
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2467
• 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
E/A	rs72646884	-1.149	0.999	N	0.669	0.388	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/A	rs72646884	-1.149	0.999	N	0.669	0.388	None	gnomAD-4.0.0	6.84278E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.09594E-06	0	1.65689E-05
E/K	rs767473022	-0.976	0.999	N	0.545	0.4	0.308278614506	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs767473022	-0.976	0.999	N	0.545	0.4	0.308278614506	gnomAD-4.0.0	1.59168E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85912E-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
E/A	0.3243	likely_benign	0.358	ambiguous	-0.72	Destabilizing	0.999	D	0.669	neutral	N	0.509493959	None	None	I
E/C	0.8828	likely_pathogenic	0.8945	pathogenic	-0.572	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
E/D	0.7026	likely_pathogenic	0.7066	pathogenic	-1.417	Destabilizing	0.999	D	0.481	neutral	N	0.489966792	None	None	I
E/F	0.8867	likely_pathogenic	0.8956	pathogenic	-0.868	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
E/G	0.5355	ambiguous	0.5702	pathogenic	-1.068	Destabilizing	1.0	D	0.753	deleterious	N	0.487333446	None	None	I
E/H	0.7723	likely_pathogenic	0.7939	pathogenic	-1.229	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
E/I	0.3626	ambiguous	0.3527	ambiguous	0.225	Stabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
E/K	0.2951	likely_benign	0.333	benign	-0.887	Destabilizing	0.999	D	0.545	neutral	N	0.518537517	None	None	I
E/L	0.6353	likely_pathogenic	0.6273	pathogenic	0.225	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
E/M	0.543	ambiguous	0.5514	ambiguous	0.747	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
E/N	0.7585	likely_pathogenic	0.7677	pathogenic	-1.161	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
E/P	0.9966	likely_pathogenic	0.9973	pathogenic	-0.068	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
E/Q	0.1519	likely_benign	0.1659	benign	-0.99	Destabilizing	1.0	D	0.622	neutral	N	0.466796428	None	None	I
E/R	0.4424	ambiguous	0.4983	ambiguous	-0.89	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/S	0.4674	ambiguous	0.4937	ambiguous	-1.586	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	I
E/T	0.4481	ambiguous	0.4717	ambiguous	-1.281	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/V	0.2071	likely_benign	0.205	benign	-0.068	Destabilizing	1.0	D	0.809	deleterious	N	0.430256811	None	None	I
E/W	0.9675	likely_pathogenic	0.9709	pathogenic	-0.994	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
E/Y	0.8721	likely_pathogenic	0.8884	pathogenic	-0.699	Destabilizing	1.0	D	0.837	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.