TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32537	97834;97835;97836	chr2:178541468;178541467;178541466	chr2:179406195;179406194;179406193
N2AB	30896	92911;92912;92913	chr2:178541468;178541467;178541466	chr2:179406195;179406194;179406193
N2A	29969	90130;90131;90132	chr2:178541468;178541467;178541466	chr2:179406195;179406194;179406193
N2B	23472	70639;70640;70641	chr2:178541468;178541467;178541466	chr2:179406195;179406194;179406193
Novex-1	23597	71014;71015;71016	chr2:178541468;178541467;178541466	chr2:179406195;179406194;179406193
Novex-2	23664	71215;71216;71217	chr2:178541468;178541467;178541466	chr2:179406195;179406194;179406193
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-125
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1379
• 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
E/K	rs1192763784	None	0.999	N	0.692	0.559	0.432826170204	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1192763784	None	0.999	N	0.692	0.559	0.432826170204	gnomAD-4.0.0	6.57376E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47029E-05	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	0.8496	likely_pathogenic	0.8807	pathogenic	-1.584	Destabilizing	0.999	D	0.705	prob.neutral	D	0.531241411	None	None	N
E/C	0.9828	likely_pathogenic	0.9836	pathogenic	-0.709	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/D	0.4782	ambiguous	0.6902	pathogenic	-1.872	Destabilizing	0.999	D	0.659	neutral	N	0.48211966	None	None	N
E/F	0.9836	likely_pathogenic	0.986	pathogenic	-1.291	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/G	0.8722	likely_pathogenic	0.9049	pathogenic	-1.957	Destabilizing	1.0	D	0.76	deleterious	D	0.526267888	None	None	N
E/H	0.9513	likely_pathogenic	0.9619	pathogenic	-1.082	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/I	0.9638	likely_pathogenic	0.9727	pathogenic	-0.507	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/K	0.9034	likely_pathogenic	0.9225	pathogenic	-1.507	Destabilizing	0.999	D	0.692	prob.neutral	N	0.507096769	None	None	N
E/L	0.9439	likely_pathogenic	0.9539	pathogenic	-0.507	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/M	0.9447	likely_pathogenic	0.9545	pathogenic	0.215	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/N	0.9303	likely_pathogenic	0.9623	pathogenic	-1.741	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/P	0.9994	likely_pathogenic	0.9996	pathogenic	-0.854	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.5644	likely_pathogenic	0.5989	pathogenic	-1.467	Destabilizing	1.0	D	0.751	deleterious	N	0.468900023	None	None	N
E/R	0.9287	likely_pathogenic	0.9408	pathogenic	-1.324	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/S	0.8438	likely_pathogenic	0.8791	pathogenic	-2.326	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
E/T	0.9263	likely_pathogenic	0.942	pathogenic	-1.966	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/V	0.9099	likely_pathogenic	0.9284	pathogenic	-0.854	Destabilizing	1.0	D	0.761	deleterious	N	0.52048099	None	None	N
E/W	0.9887	likely_pathogenic	0.9908	pathogenic	-1.37	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/Y	0.9746	likely_pathogenic	0.9788	pathogenic	-1.096	Destabilizing	1.0	D	0.809	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.