TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23930	72013;72014;72015	chr2:178574344;178574343;178574342	chr2:179439071;179439070;179439069
N2AB	22289	67090;67091;67092	chr2:178574344;178574343;178574342	chr2:179439071;179439070;179439069
N2A	21362	64309;64310;64311	chr2:178574344;178574343;178574342	chr2:179439071;179439070;179439069
N2B	14865	44818;44819;44820	chr2:178574344;178574343;178574342	chr2:179439071;179439070;179439069
Novex-1	14990	45193;45194;45195	chr2:178574344;178574343;178574342	chr2:179439071;179439070;179439069
Novex-2	15057	45394;45395;45396	chr2:178574344;178574343;178574342	chr2:179439071;179439070;179439069
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-62
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5443
• 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
K/I	rs752648041	0.46	0.984	N	0.609	0.335	0.550503487074	gnomAD-2.1.1	6.84E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.51074E-04	0
K/I	rs752648041	0.46	0.984	N	0.609	0.335	0.550503487074	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
K/I	rs752648041	0.46	0.984	N	0.609	0.335	0.550503487074	gnomAD-4.0.0	4.9582E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	1.64582E-04	6.61204E-05	0	1.60128E-05

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
K/A	0.4621	ambiguous	0.5541	ambiguous	-0.412	Destabilizing	0.919	D	0.497	neutral	None	None	None	None	N
K/C	0.6992	likely_pathogenic	0.7484	pathogenic	-0.402	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
K/D	0.8195	likely_pathogenic	0.8789	pathogenic	-0.203	Destabilizing	0.919	D	0.505	neutral	None	None	None	None	N
K/E	0.2895	likely_benign	0.3654	ambiguous	-0.141	Destabilizing	0.64	D	0.519	neutral	N	0.516844006	None	None	N
K/F	0.8286	likely_pathogenic	0.8724	pathogenic	-0.316	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	N
K/G	0.6931	likely_pathogenic	0.7784	pathogenic	-0.733	Destabilizing	0.959	D	0.518	neutral	None	None	None	None	N
K/H	0.4232	ambiguous	0.4843	ambiguous	-1.2	Destabilizing	0.988	D	0.546	neutral	None	None	None	None	N
K/I	0.3892	ambiguous	0.4681	ambiguous	0.391	Stabilizing	0.984	D	0.609	neutral	N	0.466088866	None	None	N
K/L	0.4288	ambiguous	0.4999	ambiguous	0.391	Stabilizing	0.919	D	0.518	neutral	None	None	None	None	N
K/M	0.2518	likely_benign	0.307	benign	0.401	Stabilizing	0.996	D	0.537	neutral	None	None	None	None	N
K/N	0.5615	ambiguous	0.6756	pathogenic	-0.277	Destabilizing	0.896	D	0.481	neutral	N	0.493057495	None	None	N
K/P	0.5889	likely_pathogenic	0.6384	pathogenic	0.154	Stabilizing	0.996	D	0.549	neutral	None	None	None	None	N
K/Q	0.1555	likely_benign	0.1918	benign	-0.456	Destabilizing	0.251	N	0.231	neutral	N	0.450043011	None	None	N
K/R	0.0935	likely_benign	0.0992	benign	-0.541	Destabilizing	0.011	N	0.095	neutral	N	0.436209709	None	None	N
K/S	0.5551	ambiguous	0.6581	pathogenic	-0.873	Destabilizing	0.919	D	0.469	neutral	None	None	None	None	N
K/T	0.2213	likely_benign	0.2899	benign	-0.627	Destabilizing	0.946	D	0.502	neutral	N	0.44454119	None	None	N
K/V	0.3923	ambiguous	0.4641	ambiguous	0.154	Stabilizing	0.988	D	0.506	neutral	None	None	None	None	N
K/W	0.8761	likely_pathogenic	0.9009	pathogenic	-0.208	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
K/Y	0.7183	likely_pathogenic	0.7709	pathogenic	0.103	Stabilizing	0.996	D	0.6	neutral	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.