TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7056	21391;21392;21393	chr2:178724093;178724092;178724091	chr2:179588820;179588819;179588818
N2AB	6739	20440;20441;20442	chr2:178724093;178724092;178724091	chr2:179588820;179588819;179588818
N2A	5812	17659;17660;17661	chr2:178724093;178724092;178724091	chr2:179588820;179588819;179588818
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-55
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.6878
• Predicted PPI site: I

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	rs1306079131	None	0.031	N	0.237	0.107	0.381916209588	gnomAD-4.0.0	6.84436E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99658E-07	0	0
V/M	rs1306079131	None	0.782	D	0.343	0.134	0.493089126863	gnomAD-4.0.0	1.36887E-06	None	None	None	None	I	None	0	0	None	0	2.52232E-05	None	0	0	8.99658E-07	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	0.131	likely_benign	0.1366	benign	-0.581	Destabilizing	0.003	N	0.205	neutral	N	0.484225447	None	None	I
V/C	0.5999	likely_pathogenic	0.5966	pathogenic	-0.764	Destabilizing	0.991	D	0.411	neutral	None	None	None	None	I
V/D	0.1967	likely_benign	0.2137	benign	-0.014	Destabilizing	0.906	D	0.555	neutral	None	None	None	None	I
V/E	0.1851	likely_benign	0.1875	benign	-0.093	Destabilizing	0.782	D	0.51	neutral	D	0.522031687	None	None	I
V/F	0.0882	likely_benign	0.0873	benign	-0.571	Destabilizing	0.826	D	0.417	neutral	None	None	None	None	I
V/G	0.1403	likely_benign	0.1445	benign	-0.758	Destabilizing	0.338	N	0.514	neutral	N	0.492680996	None	None	I
V/H	0.3493	ambiguous	0.3522	ambiguous	-0.232	Destabilizing	0.991	D	0.559	neutral	None	None	None	None	I
V/I	0.0655	likely_benign	0.0658	benign	-0.25	Destabilizing	0.002	N	0.185	neutral	None	None	None	None	I
V/K	0.2024	likely_benign	0.2032	benign	-0.5	Destabilizing	0.826	D	0.516	neutral	None	None	None	None	I
V/L	0.1052	likely_benign	0.1056	benign	-0.25	Destabilizing	0.031	N	0.237	neutral	N	0.457713637	None	None	I
V/M	0.0994	likely_benign	0.0942	benign	-0.388	Destabilizing	0.782	D	0.343	neutral	D	0.530864601	None	None	I
V/N	0.1396	likely_benign	0.1481	benign	-0.321	Destabilizing	0.906	D	0.556	neutral	None	None	None	None	I
V/P	0.3589	ambiguous	0.3686	ambiguous	-0.324	Destabilizing	0.906	D	0.539	neutral	None	None	None	None	I
V/Q	0.1924	likely_benign	0.1895	benign	-0.501	Destabilizing	0.906	D	0.536	neutral	None	None	None	None	I
V/R	0.168	likely_benign	0.172	benign	-0.035	Destabilizing	0.906	D	0.556	neutral	None	None	None	None	I
V/S	0.1294	likely_benign	0.1373	benign	-0.783	Destabilizing	0.404	N	0.497	neutral	None	None	None	None	I
V/T	0.1388	likely_benign	0.1432	benign	-0.751	Destabilizing	0.575	D	0.316	neutral	None	None	None	None	I
V/W	0.6333	likely_pathogenic	0.6026	pathogenic	-0.657	Destabilizing	0.991	D	0.627	neutral	None	None	None	None	I
V/Y	0.3183	likely_benign	0.3153	benign	-0.363	Destabilizing	0.906	D	0.403	neutral	None	None	None	None	I

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.