TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26950	81073;81074;81075	chr2:178565284;178565283;178565282	chr2:179430011;179430010;179430009
N2AB	25309	76150;76151;76152	chr2:178565284;178565283;178565282	chr2:179430011;179430010;179430009
N2A	24382	73369;73370;73371	chr2:178565284;178565283;178565282	chr2:179430011;179430010;179430009
N2B	17885	53878;53879;53880	chr2:178565284;178565283;178565282	chr2:179430011;179430010;179430009
Novex-1	18010	54253;54254;54255	chr2:178565284;178565283;178565282	chr2:179430011;179430010;179430009
Novex-2	18077	54454;54455;54456	chr2:178565284;178565283;178565282	chr2:179430011;179430010;179430009
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-139
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.195
• 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
Y/H	rs1705314852	None	1.0	D	0.795	0.836	0.760680927031	gnomAD-4.0.0	9.54949E-06	None	None	None	None	N	None	0	0	None	0	1.66454E-04	None	0	0	0	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
Y/A	0.9988	likely_pathogenic	0.9984	pathogenic	-2.425	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
Y/C	0.9837	likely_pathogenic	0.977	pathogenic	-1.784	Destabilizing	1.0	D	0.816	deleterious	D	0.650173091	None	None	N
Y/D	0.9987	likely_pathogenic	0.9986	pathogenic	-2.757	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.666424616	None	None	N
Y/E	0.9995	likely_pathogenic	0.9994	pathogenic	-2.51	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/F	0.3328	likely_benign	0.2917	benign	-0.811	Destabilizing	0.999	D	0.694	prob.neutral	D	0.601288149	None	None	N
Y/G	0.9963	likely_pathogenic	0.9952	pathogenic	-2.888	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/H	0.9916	likely_pathogenic	0.988	pathogenic	-2.002	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.666222812	None	None	N
Y/I	0.9655	likely_pathogenic	0.9563	pathogenic	-0.899	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
Y/K	0.9995	likely_pathogenic	0.9993	pathogenic	-1.858	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/L	0.9368	likely_pathogenic	0.9174	pathogenic	-0.899	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
Y/M	0.9855	likely_pathogenic	0.9816	pathogenic	-0.981	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
Y/N	0.9927	likely_pathogenic	0.9909	pathogenic	-2.733	Highly Destabilizing	1.0	D	0.828	deleterious	D	0.666424616	None	None	N
Y/P	0.9997	likely_pathogenic	0.9996	pathogenic	-1.422	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/Q	0.9995	likely_pathogenic	0.9993	pathogenic	-2.319	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
Y/R	0.9984	likely_pathogenic	0.9979	pathogenic	-2.002	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/S	0.9975	likely_pathogenic	0.9967	pathogenic	-3.143	Highly Destabilizing	1.0	D	0.844	deleterious	D	0.666424616	None	None	N
Y/T	0.9986	likely_pathogenic	0.9981	pathogenic	-2.749	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/V	0.9619	likely_pathogenic	0.9527	pathogenic	-1.422	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
Y/W	0.8911	likely_pathogenic	0.8594	pathogenic	-0.154	Destabilizing	1.0	D	0.784	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.