TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5227	15904;15905;15906	chr2:178733710;178733709;178733708	chr2:179598437;179598436;179598435
N2AB	4910	14953;14954;14955	chr2:178733710;178733709;178733708	chr2:179598437;179598436;179598435
N2A	3983	12172;12173;12174	chr2:178733710;178733709;178733708	chr2:179598437;179598436;179598435
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-35
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0796
• 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
I/F	None	None	0.998	D	0.753	0.637	0.79036882002	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	None	0	0	0	0	0
I/V	rs2080946599	None	0.333	D	0.261	0.304	0.64021514727	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs2080946599	None	0.333	D	0.261	0.304	0.64021514727	gnomAD-4.0.0	6.57117E-06	None	None	None	None	N	None	2.41231E-05	0	None	0	0	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
I/A	0.8466	likely_pathogenic	0.8994	pathogenic	-2.258	Highly Destabilizing	0.992	D	0.709	prob.delet.	None	None	None	None	N
I/C	0.8939	likely_pathogenic	0.9349	pathogenic	-1.66	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
I/D	0.9755	likely_pathogenic	0.9873	pathogenic	-2.45	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
I/E	0.956	likely_pathogenic	0.9752	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
I/F	0.1921	likely_benign	0.2311	benign	-1.266	Destabilizing	0.998	D	0.753	deleterious	D	0.543574147	None	None	N
I/G	0.9657	likely_pathogenic	0.9781	pathogenic	-2.831	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
I/H	0.8641	likely_pathogenic	0.9179	pathogenic	-2.329	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
I/K	0.8992	likely_pathogenic	0.9401	pathogenic	-1.879	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
I/L	0.1322	likely_benign	0.1569	benign	-0.601	Destabilizing	0.889	D	0.415	neutral	D	0.543232098	None	None	N
I/M	0.1781	likely_benign	0.2259	benign	-0.617	Destabilizing	0.998	D	0.705	prob.neutral	D	0.697998429	None	None	N
I/N	0.7875	likely_pathogenic	0.8571	pathogenic	-2.322	Highly Destabilizing	0.999	D	0.889	deleterious	D	0.824098718	None	None	N
I/P	0.9802	likely_pathogenic	0.9883	pathogenic	-1.134	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
I/Q	0.8908	likely_pathogenic	0.934	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
I/R	0.8573	likely_pathogenic	0.9124	pathogenic	-1.738	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
I/S	0.811	likely_pathogenic	0.8729	pathogenic	-3.028	Highly Destabilizing	0.998	D	0.861	deleterious	D	0.824098718	None	None	N
I/T	0.8353	likely_pathogenic	0.8917	pathogenic	-2.603	Highly Destabilizing	0.989	D	0.778	deleterious	D	0.824322788	None	None	N
I/V	0.1582	likely_benign	0.1915	benign	-1.134	Destabilizing	0.333	N	0.261	neutral	D	0.545259897	None	None	N
I/W	0.9145	likely_pathogenic	0.9442	pathogenic	-1.655	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
I/Y	0.718	likely_pathogenic	0.7749	pathogenic	-1.327	Destabilizing	1.0	D	0.776	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.