TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19108	57547;57548;57549	chr2:178597760;178597759;178597758	chr2:179462487;179462486;179462485
N2AB	17467	52624;52625;52626	chr2:178597760;178597759;178597758	chr2:179462487;179462486;179462485
N2A	16540	49843;49844;49845	chr2:178597760;178597759;178597758	chr2:179462487;179462486;179462485
N2B	10043	30352;30353;30354	chr2:178597760;178597759;178597758	chr2:179462487;179462486;179462485
Novex-1	10168	30727;30728;30729	chr2:178597760;178597759;178597758	chr2:179462487;179462486;179462485
Novex-2	10235	30928;30929;30930	chr2:178597760;178597759;178597758	chr2:179462487;179462486;179462485
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-117
• Domain position: 14
• Structural Position: 25
• Q(SASA): 0.1591
• 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
G/E	rs774910035	-1.71	0.999	N	0.739	0.365	0.356484672536	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
G/E	rs774910035	-1.71	0.999	N	0.739	0.365	0.356484672536	gnomAD-4.0.0	2.53246E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.23868E-05	1.15961E-05	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
G/A	0.1806	likely_benign	0.2783	benign	-0.569	Destabilizing	0.767	D	0.453	neutral	N	0.499383248	None	None	N
G/C	0.3613	ambiguous	0.4707	ambiguous	-0.967	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
G/D	0.5778	likely_pathogenic	0.7452	pathogenic	-0.956	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
G/E	0.5629	ambiguous	0.7328	pathogenic	-1.097	Destabilizing	0.999	D	0.739	prob.delet.	N	0.426709499	None	None	N
G/F	0.8751	likely_pathogenic	0.9323	pathogenic	-1.224	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
G/H	0.673	likely_pathogenic	0.8094	pathogenic	-0.922	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/I	0.7603	likely_pathogenic	0.8484	pathogenic	-0.537	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
G/K	0.6967	likely_pathogenic	0.8521	pathogenic	-1.073	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
G/L	0.7539	likely_pathogenic	0.8584	pathogenic	-0.537	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
G/M	0.6835	likely_pathogenic	0.7834	pathogenic	-0.391	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
G/N	0.4532	ambiguous	0.5891	pathogenic	-0.712	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
G/P	0.9934	likely_pathogenic	0.9963	pathogenic	-0.512	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
G/Q	0.5281	ambiguous	0.6825	pathogenic	-1.019	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
G/R	0.5765	likely_pathogenic	0.7778	pathogenic	-0.607	Destabilizing	0.999	D	0.761	deleterious	N	0.502615554	None	None	N
G/S	0.1296	likely_benign	0.1898	benign	-0.896	Destabilizing	0.967	D	0.453	neutral	None	None	None	None	N
G/T	0.3151	likely_benign	0.4046	ambiguous	-0.969	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
G/V	0.5707	likely_pathogenic	0.7123	pathogenic	-0.512	Destabilizing	0.999	D	0.724	prob.delet.	N	0.479254099	None	None	N
G/W	0.7997	likely_pathogenic	0.8806	pathogenic	-1.404	Destabilizing	1.0	D	0.753	deleterious	N	0.479507588	None	None	N
G/Y	0.7746	likely_pathogenic	0.8694	pathogenic	-1.049	Destabilizing	1.0	D	0.755	deleterious	None	None	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.