TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31370	94333;94334;94335	chr2:178547518;178547517;178547516	chr2:179412245;179412244;179412243
N2AB	29729	89410;89411;89412	chr2:178547518;178547517;178547516	chr2:179412245;179412244;179412243
N2A	28802	86629;86630;86631	chr2:178547518;178547517;178547516	chr2:179412245;179412244;179412243
N2B	22305	67138;67139;67140	chr2:178547518;178547517;178547516	chr2:179412245;179412244;179412243
Novex-1	22430	67513;67514;67515	chr2:178547518;178547517;178547516	chr2:179412245;179412244;179412243
Novex-2	22497	67714;67715;67716	chr2:178547518;178547517;178547516	chr2:179412245;179412244;179412243
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-116
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1293
• 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
V/L	rs568049899	-0.398	0.114	N	0.582	0.131	0.413761986042	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92678E-04	None	0	0	0	0	0
V/L	rs568049899	-0.398	0.114	N	0.582	0.131	0.413761986042	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
V/L	rs568049899	-0.398	0.114	N	0.582	0.131	0.413761986042	gnomAD-4.0.0	6.56685E-06	None	None	None	None	N	None	0	0	None	0	1.93125E-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
V/A	0.7629	likely_pathogenic	0.7594	pathogenic	-1.844	Destabilizing	0.645	D	0.641	neutral	N	0.48227838	None	None	N
V/C	0.9482	likely_pathogenic	0.9463	pathogenic	-1.461	Destabilizing	0.995	D	0.767	deleterious	None	None	None	None	N
V/D	0.9973	likely_pathogenic	0.9956	pathogenic	-2.135	Highly Destabilizing	0.928	D	0.832	deleterious	N	0.50219306	None	None	N
V/E	0.99	likely_pathogenic	0.9847	pathogenic	-1.912	Destabilizing	0.981	D	0.808	deleterious	None	None	None	None	N
V/F	0.8315	likely_pathogenic	0.7921	pathogenic	-1.075	Destabilizing	0.864	D	0.768	deleterious	N	0.50886165	None	None	N
V/G	0.9356	likely_pathogenic	0.9235	pathogenic	-2.389	Highly Destabilizing	0.928	D	0.838	deleterious	D	0.539162039	None	None	N
V/H	0.9969	likely_pathogenic	0.995	pathogenic	-2.077	Highly Destabilizing	0.995	D	0.84	deleterious	None	None	None	None	N
V/I	0.105	likely_benign	0.101	benign	-0.333	Destabilizing	0.006	N	0.177	neutral	N	0.492220494	None	None	N
V/K	0.9945	likely_pathogenic	0.9919	pathogenic	-1.602	Destabilizing	0.945	D	0.812	deleterious	None	None	None	None	N
V/L	0.732	likely_pathogenic	0.6911	pathogenic	-0.333	Destabilizing	0.114	N	0.582	neutral	N	0.464403344	None	None	N
V/M	0.675	likely_pathogenic	0.6359	pathogenic	-0.406	Destabilizing	0.894	D	0.725	prob.delet.	None	None	None	None	N
V/N	0.9892	likely_pathogenic	0.9843	pathogenic	-1.92	Destabilizing	0.981	D	0.868	deleterious	None	None	None	None	N
V/P	0.9916	likely_pathogenic	0.9895	pathogenic	-0.807	Destabilizing	0.981	D	0.807	deleterious	None	None	None	None	N
V/Q	0.9902	likely_pathogenic	0.9857	pathogenic	-1.732	Destabilizing	0.981	D	0.847	deleterious	None	None	None	None	N
V/R	0.9915	likely_pathogenic	0.9878	pathogenic	-1.494	Destabilizing	0.945	D	0.871	deleterious	None	None	None	None	N
V/S	0.9584	likely_pathogenic	0.9501	pathogenic	-2.581	Highly Destabilizing	0.945	D	0.812	deleterious	None	None	None	None	N
V/T	0.9171	likely_pathogenic	0.9016	pathogenic	-2.194	Highly Destabilizing	0.707	D	0.689	prob.neutral	None	None	None	None	N
V/W	0.9974	likely_pathogenic	0.9961	pathogenic	-1.531	Destabilizing	0.995	D	0.825	deleterious	None	None	None	None	N
V/Y	0.9827	likely_pathogenic	0.9762	pathogenic	-1.117	Destabilizing	0.945	D	0.763	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.