TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24816	74671;74672;74673	chr2:178571686;178571685;178571684	chr2:179436413;179436412;179436411
N2AB	23175	69748;69749;69750	chr2:178571686;178571685;178571684	chr2:179436413;179436412;179436411
N2A	22248	66967;66968;66969	chr2:178571686;178571685;178571684	chr2:179436413;179436412;179436411
N2B	15751	47476;47477;47478	chr2:178571686;178571685;178571684	chr2:179436413;179436412;179436411
Novex-1	15876	47851;47852;47853	chr2:178571686;178571685;178571684	chr2:179436413;179436412;179436411
Novex-2	15943	48052;48053;48054	chr2:178571686;178571685;178571684	chr2:179436413;179436412;179436411
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-68
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.2476
• 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/I	rs1304130047	-0.251	0.003	N	0.195	0.084	0.285698343383	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
V/I	rs1304130047	-0.251	0.003	N	0.195	0.084	0.285698343383	gnomAD-4.0.0	1.5919E-06	None	None	None	None	N	None	0	0	None	0	2.7767E-05	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	0.7224	likely_pathogenic	0.7297	pathogenic	-1.656	Destabilizing	0.517	D	0.627	neutral	N	0.504444331	None	None	N
V/C	0.9166	likely_pathogenic	0.9182	pathogenic	-1.259	Destabilizing	0.996	D	0.694	prob.neutral	None	None	None	None	N
V/D	0.9895	likely_pathogenic	0.9893	pathogenic	-1.49	Destabilizing	0.983	D	0.819	deleterious	D	0.531031283	None	None	N
V/E	0.9721	likely_pathogenic	0.9711	pathogenic	-1.351	Destabilizing	0.987	D	0.775	deleterious	None	None	None	None	N
V/F	0.6564	likely_pathogenic	0.6309	pathogenic	-0.954	Destabilizing	0.901	D	0.691	prob.neutral	N	0.485326118	None	None	N
V/G	0.8804	likely_pathogenic	0.8823	pathogenic	-2.128	Highly Destabilizing	0.949	D	0.797	deleterious	D	0.531791751	None	None	N
V/H	0.9916	likely_pathogenic	0.9913	pathogenic	-1.809	Destabilizing	0.996	D	0.838	deleterious	None	None	None	None	N
V/I	0.082	likely_benign	0.0795	benign	-0.396	Destabilizing	0.003	N	0.195	neutral	N	0.484198444	None	None	N
V/K	0.981	likely_pathogenic	0.9797	pathogenic	-1.374	Destabilizing	0.961	D	0.776	deleterious	None	None	None	None	N
V/L	0.3299	likely_benign	0.3224	benign	-0.396	Destabilizing	0.075	N	0.467	neutral	N	0.462427944	None	None	N
V/M	0.454	ambiguous	0.4331	ambiguous	-0.451	Destabilizing	0.923	D	0.624	neutral	None	None	None	None	N
V/N	0.9657	likely_pathogenic	0.9653	pathogenic	-1.408	Destabilizing	0.987	D	0.825	deleterious	None	None	None	None	N
V/P	0.8428	likely_pathogenic	0.8533	pathogenic	-0.783	Destabilizing	0.987	D	0.786	deleterious	None	None	None	None	N
V/Q	0.9719	likely_pathogenic	0.97	pathogenic	-1.341	Destabilizing	0.987	D	0.797	deleterious	None	None	None	None	N
V/R	0.9704	likely_pathogenic	0.9695	pathogenic	-1.17	Destabilizing	0.987	D	0.826	deleterious	None	None	None	None	N
V/S	0.9103	likely_pathogenic	0.9143	pathogenic	-2.077	Highly Destabilizing	0.961	D	0.733	prob.delet.	None	None	None	None	N
V/T	0.835	likely_pathogenic	0.832	pathogenic	-1.795	Destabilizing	0.775	D	0.645	neutral	None	None	None	None	N
V/W	0.9898	likely_pathogenic	0.9882	pathogenic	-1.321	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
V/Y	0.9592	likely_pathogenic	0.9577	pathogenic	-0.95	Destabilizing	0.961	D	0.686	prob.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.