TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26329	79210;79211;79212	chr2:178567147;178567146;178567145	chr2:179431874;179431873;179431872
N2AB	24688	74287;74288;74289	chr2:178567147;178567146;178567145	chr2:179431874;179431873;179431872
N2A	23761	71506;71507;71508	chr2:178567147;178567146;178567145	chr2:179431874;179431873;179431872
N2B	17264	52015;52016;52017	chr2:178567147;178567146;178567145	chr2:179431874;179431873;179431872
Novex-1	17389	52390;52391;52392	chr2:178567147;178567146;178567145	chr2:179431874;179431873;179431872
Novex-2	17456	52591;52592;52593	chr2:178567147;178567146;178567145	chr2:179431874;179431873;179431872
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-79
• Domain position: 44
• Structural Position: 50
• Q(SASA): 0.2874
• 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/A	rs1443062175	-0.985	0.825	N	0.534	0.325	0.201204373187	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
T/A	rs1443062175	-0.985	0.825	N	0.534	0.325	0.201204373187	gnomAD-4.0.0	1.36865E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79919E-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
T/A	0.4867	ambiguous	0.4923	ambiguous	-0.671	Destabilizing	0.825	D	0.534	neutral	N	0.514401134	None	None	N
T/C	0.9356	likely_pathogenic	0.9422	pathogenic	-0.464	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
T/D	0.9589	likely_pathogenic	0.9513	pathogenic	0.059	Stabilizing	0.991	D	0.579	neutral	None	None	None	None	N
T/E	0.9554	likely_pathogenic	0.9418	pathogenic	0.034	Stabilizing	0.991	D	0.575	neutral	None	None	None	None	N
T/F	0.9631	likely_pathogenic	0.9597	pathogenic	-0.81	Destabilizing	0.995	D	0.716	prob.delet.	None	None	None	None	N
T/G	0.8039	likely_pathogenic	0.7791	pathogenic	-0.895	Destabilizing	0.938	D	0.59	neutral	None	None	None	None	N
T/H	0.9468	likely_pathogenic	0.9408	pathogenic	-1.119	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
T/I	0.8897	likely_pathogenic	0.8865	pathogenic	-0.177	Destabilizing	0.994	D	0.669	neutral	N	0.466862561	None	None	N
T/K	0.91	likely_pathogenic	0.8815	pathogenic	-0.645	Destabilizing	0.991	D	0.58	neutral	None	None	None	None	N
T/L	0.6513	likely_pathogenic	0.649	pathogenic	-0.177	Destabilizing	0.968	D	0.544	neutral	None	None	None	None	N
T/M	0.4443	ambiguous	0.4496	ambiguous	0.02	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
T/N	0.7147	likely_pathogenic	0.6737	pathogenic	-0.496	Destabilizing	0.988	D	0.636	neutral	N	0.471648727	None	None	N
T/P	0.8566	likely_pathogenic	0.8135	pathogenic	-0.31	Destabilizing	0.994	D	0.659	neutral	N	0.516692077	None	None	N
T/Q	0.9184	likely_pathogenic	0.8984	pathogenic	-0.685	Destabilizing	0.991	D	0.674	neutral	None	None	None	None	N
T/R	0.8973	likely_pathogenic	0.8758	pathogenic	-0.371	Destabilizing	0.991	D	0.65	neutral	None	None	None	None	N
T/S	0.4352	ambiguous	0.4223	ambiguous	-0.794	Destabilizing	0.234	N	0.302	neutral	N	0.484945018	None	None	N
T/V	0.7145	likely_pathogenic	0.7163	pathogenic	-0.31	Destabilizing	0.968	D	0.567	neutral	None	None	None	None	N
T/W	0.9912	likely_pathogenic	0.9898	pathogenic	-0.735	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
T/Y	0.9627	likely_pathogenic	0.9581	pathogenic	-0.508	Destabilizing	0.998	D	0.71	prob.delet.	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.