TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30601	92026;92027;92028	chr2:178550037;178550036;178550035	chr2:179414764;179414763;179414762
N2AB	28960	87103;87104;87105	chr2:178550037;178550036;178550035	chr2:179414764;179414763;179414762
N2A	28033	84322;84323;84324	chr2:178550037;178550036;178550035	chr2:179414764;179414763;179414762
N2B	21536	64831;64832;64833	chr2:178550037;178550036;178550035	chr2:179414764;179414763;179414762
Novex-1	21661	65206;65207;65208	chr2:178550037;178550036;178550035	chr2:179414764;179414763;179414762
Novex-2	21728	65407;65408;65409	chr2:178550037;178550036;178550035	chr2:179414764;179414763;179414762
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-149
• Domain position: 70
• Structural Position: 158
• Q(SASA): 0.1218
• 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
A/T	None	None	1.0	D	0.729	0.751	0.67724314777	gnomAD-4.0.0	2.05528E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73792E-04	1.80086E-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
A/C	0.6811	likely_pathogenic	0.6641	pathogenic	-1.039	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/D	0.996	likely_pathogenic	0.9954	pathogenic	-1.697	Destabilizing	1.0	D	0.848	deleterious	D	0.645733397	None	None	N
A/E	0.99	likely_pathogenic	0.9874	pathogenic	-1.747	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
A/F	0.9638	likely_pathogenic	0.962	pathogenic	-1.168	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/G	0.2453	likely_benign	0.2622	benign	-1.271	Destabilizing	1.0	D	0.549	neutral	D	0.58102018	None	None	N
A/H	0.9968	likely_pathogenic	0.9958	pathogenic	-1.453	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/I	0.6599	likely_pathogenic	0.6618	pathogenic	-0.531	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
A/K	0.9978	likely_pathogenic	0.997	pathogenic	-1.414	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/L	0.6102	likely_pathogenic	0.5871	pathogenic	-0.531	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
A/M	0.7564	likely_pathogenic	0.7456	pathogenic	-0.381	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/N	0.9863	likely_pathogenic	0.9838	pathogenic	-1.104	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
A/P	0.9958	likely_pathogenic	0.9958	pathogenic	-0.658	Destabilizing	1.0	D	0.835	deleterious	D	0.629512231	None	None	N
A/Q	0.9855	likely_pathogenic	0.9812	pathogenic	-1.323	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/R	0.9939	likely_pathogenic	0.9922	pathogenic	-0.994	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
A/S	0.3671	ambiguous	0.3573	ambiguous	-1.382	Destabilizing	1.0	D	0.55	neutral	D	0.613089262	None	None	N
A/T	0.4254	ambiguous	0.4147	ambiguous	-1.353	Destabilizing	1.0	D	0.729	prob.delet.	D	0.644926179	None	None	N
A/V	0.3066	likely_benign	0.308	benign	-0.658	Destabilizing	1.0	D	0.608	neutral	N	0.495111575	None	None	N
A/W	0.9978	likely_pathogenic	0.9975	pathogenic	-1.485	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/Y	0.9899	likely_pathogenic	0.9878	pathogenic	-1.131	Destabilizing	1.0	D	0.859	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.