TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26300	79123;79124;79125	chr2:178567234;178567233;178567232	chr2:179431961;179431960;179431959
N2AB	24659	74200;74201;74202	chr2:178567234;178567233;178567232	chr2:179431961;179431960;179431959
N2A	23732	71419;71420;71421	chr2:178567234;178567233;178567232	chr2:179431961;179431960;179431959
N2B	17235	51928;51929;51930	chr2:178567234;178567233;178567232	chr2:179431961;179431960;179431959
Novex-1	17360	52303;52304;52305	chr2:178567234;178567233;178567232	chr2:179431961;179431960;179431959
Novex-2	17427	52504;52505;52506	chr2:178567234;178567233;178567232	chr2:179431961;179431960;179431959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-79
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.2805
• 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
T/N	rs750541239	-0.622	0.988	N	0.702	0.469	0.419835214384	gnomAD-2.1.1	2.05E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.52E-05	0
T/N	rs750541239	-0.622	0.988	N	0.702	0.469	0.419835214384	gnomAD-4.0.0	1.51092E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.98417E-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
T/A	0.3107	likely_benign	0.2819	benign	-0.603	Destabilizing	0.825	D	0.465	neutral	N	0.490757395	None	None	N
T/C	0.6899	likely_pathogenic	0.692	pathogenic	-0.533	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
T/D	0.7964	likely_pathogenic	0.7873	pathogenic	-1.347	Destabilizing	0.991	D	0.698	prob.neutral	None	None	None	None	N
T/E	0.8996	likely_pathogenic	0.8865	pathogenic	-1.331	Destabilizing	0.991	D	0.705	prob.neutral	None	None	None	None	N
T/F	0.6151	likely_pathogenic	0.5683	pathogenic	-0.729	Destabilizing	0.995	D	0.793	deleterious	None	None	None	None	N
T/G	0.388	ambiguous	0.3891	ambiguous	-0.869	Destabilizing	0.938	D	0.613	neutral	None	None	None	None	N
T/H	0.6154	likely_pathogenic	0.6071	pathogenic	-1.27	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
T/I	0.8126	likely_pathogenic	0.751	pathogenic	0.019	Stabilizing	0.994	D	0.776	deleterious	N	0.517699968	None	None	N
T/K	0.7979	likely_pathogenic	0.796	pathogenic	-0.855	Destabilizing	0.991	D	0.706	prob.neutral	None	None	None	None	N
T/L	0.3434	ambiguous	0.2818	benign	0.019	Stabilizing	0.968	D	0.609	neutral	None	None	None	None	N
T/M	0.2357	likely_benign	0.2085	benign	0.417	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
T/N	0.2822	likely_benign	0.2622	benign	-1.042	Destabilizing	0.988	D	0.702	prob.neutral	N	0.476372442	None	None	N
T/P	0.8443	likely_pathogenic	0.8259	pathogenic	-0.156	Destabilizing	0.994	D	0.771	deleterious	D	0.522308324	None	None	N
T/Q	0.6946	likely_pathogenic	0.6767	pathogenic	-1.257	Destabilizing	0.991	D	0.757	deleterious	None	None	None	None	N
T/R	0.7303	likely_pathogenic	0.7267	pathogenic	-0.57	Destabilizing	0.991	D	0.762	deleterious	None	None	None	None	N
T/S	0.1508	likely_benign	0.1494	benign	-1.108	Destabilizing	0.234	N	0.35	neutral	N	0.454374182	None	None	N
T/V	0.6198	likely_pathogenic	0.561	ambiguous	-0.156	Destabilizing	0.968	D	0.553	neutral	None	None	None	None	N
T/W	0.9066	likely_pathogenic	0.8828	pathogenic	-0.78	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
T/Y	0.6712	likely_pathogenic	0.6483	pathogenic	-0.474	Destabilizing	0.998	D	0.793	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.