TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16894	50905;50906;50907	chr2:178611549;178611548;178611547	chr2:179476276;179476275;179476274
N2AB	15253	45982;45983;45984	chr2:178611549;178611548;178611547	chr2:179476276;179476275;179476274
N2A	14326	43201;43202;43203	chr2:178611549;178611548;178611547	chr2:179476276;179476275;179476274
N2B	7829	23710;23711;23712	chr2:178611549;178611548;178611547	chr2:179476276;179476275;179476274
Novex-1	7954	24085;24086;24087	chr2:178611549;178611548;178611547	chr2:179476276;179476275;179476274
Novex-2	8021	24286;24287;24288	chr2:178611549;178611548;178611547	chr2:179476276;179476275;179476274
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-11
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3701
• 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/A	rs1270525854	-0.957	0.001	N	0.159	0.116	0.243972157842	gnomAD-2.1.1	7.17E-06	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	0	7.87E-06	0
V/A	rs1270525854	-0.957	0.001	N	0.159	0.116	0.243972157842	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs1270525854	-0.957	0.001	N	0.159	0.116	0.243972157842	gnomAD-4.0.0	4.33989E-06	None	None	None	None	N	None	1.33561E-05	0	None	0	2.23584E-05	None	0	0	4.23967E-06	0	0
V/I	rs754878640	-0.452	0.517	N	0.404	0.162	0.290590437066	gnomAD-2.1.1	7.17E-06	None	None	None	None	N	None	0	2.83E-05	None	0	0	None	0	None	0	7.87E-06	0
V/I	rs754878640	-0.452	0.517	N	0.404	0.162	0.290590437066	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs754878640	-0.452	0.517	N	0.404	0.162	0.290590437066	gnomAD-4.0.0	1.23998E-06	None	None	None	None	N	None	0	1.66839E-05	None	0	0	None	0	0	8.47939E-07	0	0
V/L	rs754878640	-0.408	0.349	N	0.396	0.165	0.207176502487	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
V/L	rs754878640	-0.408	0.349	N	0.396	0.165	0.207176502487	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs754878640	-0.408	0.349	N	0.396	0.165	0.207176502487	gnomAD-4.0.0	4.33992E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08763E-06	0	1.60226E-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
V/A	0.1073	likely_benign	0.1044	benign	-1.187	Destabilizing	0.001	N	0.159	neutral	N	0.392961708	None	None	N
V/C	0.8078	likely_pathogenic	0.8129	pathogenic	-0.72	Destabilizing	0.989	D	0.523	neutral	None	None	None	None	N
V/D	0.5263	ambiguous	0.4511	ambiguous	-1.044	Destabilizing	0.961	D	0.659	neutral	None	None	None	None	N
V/E	0.3461	ambiguous	0.3091	benign	-1.117	Destabilizing	0.901	D	0.577	neutral	N	0.441240522	None	None	N
V/F	0.2941	likely_benign	0.2623	benign	-1.136	Destabilizing	0.961	D	0.524	neutral	None	None	None	None	N
V/G	0.2771	likely_benign	0.2415	benign	-1.416	Destabilizing	0.565	D	0.549	neutral	N	0.433492316	None	None	N
V/H	0.6947	likely_pathogenic	0.6631	pathogenic	-0.972	Destabilizing	0.996	D	0.66	neutral	None	None	None	None	N
V/I	0.089	likely_benign	0.0909	benign	-0.693	Destabilizing	0.517	D	0.404	neutral	N	0.45872428	None	None	N
V/K	0.3526	ambiguous	0.3138	benign	-1.026	Destabilizing	0.923	D	0.586	neutral	None	None	None	None	N
V/L	0.2416	likely_benign	0.2418	benign	-0.693	Destabilizing	0.349	N	0.396	neutral	N	0.457337303	None	None	N
V/M	0.1676	likely_benign	0.1664	benign	-0.443	Destabilizing	0.987	D	0.485	neutral	None	None	None	None	N
V/N	0.3452	ambiguous	0.3151	benign	-0.714	Destabilizing	0.961	D	0.664	neutral	None	None	None	None	N
V/P	0.6245	likely_pathogenic	0.5385	ambiguous	-0.823	Destabilizing	0.961	D	0.635	neutral	None	None	None	None	N
V/Q	0.3614	ambiguous	0.3464	ambiguous	-0.975	Destabilizing	0.961	D	0.649	neutral	None	None	None	None	N
V/R	0.357	ambiguous	0.3164	benign	-0.409	Destabilizing	0.923	D	0.663	neutral	None	None	None	None	N
V/S	0.191	likely_benign	0.1823	benign	-1.123	Destabilizing	0.633	D	0.553	neutral	None	None	None	None	N
V/T	0.1624	likely_benign	0.1594	benign	-1.099	Destabilizing	0.775	D	0.386	neutral	None	None	None	None	N
V/W	0.9282	likely_pathogenic	0.9122	pathogenic	-1.254	Destabilizing	0.996	D	0.698	prob.neutral	None	None	None	None	N
V/Y	0.7368	likely_pathogenic	0.7045	pathogenic	-0.987	Destabilizing	0.987	D	0.514	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.