TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19818	59677;59678;59679	chr2:178592553;178592552;178592551	chr2:179457280;179457279;179457278
N2AB	18177	54754;54755;54756	chr2:178592553;178592552;178592551	chr2:179457280;179457279;179457278
N2A	17250	51973;51974;51975	chr2:178592553;178592552;178592551	chr2:179457280;179457279;179457278
N2B	10753	32482;32483;32484	chr2:178592553;178592552;178592551	chr2:179457280;179457279;179457278
Novex-1	10878	32857;32858;32859	chr2:178592553;178592552;178592551	chr2:179457280;179457279;179457278
Novex-2	10945	33058;33059;33060	chr2:178592553;178592552;178592551	chr2:179457280;179457279;179457278
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: Ig-119
• Domain position: 29
• Structural Position: 46
• Q(SASA): 0.1839
• 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/G	rs1371676567	-2.593	1.0	D	0.878	0.836	0.884655929374	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	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	0.5977	likely_pathogenic	0.6383	pathogenic	-1.854	Destabilizing	0.998	D	0.648	neutral	D	0.558298404	None	None	N
V/C	0.9156	likely_pathogenic	0.9227	pathogenic	-1.253	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/D	0.9848	likely_pathogenic	0.991	pathogenic	-2.228	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/E	0.9635	likely_pathogenic	0.9758	pathogenic	-2.051	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.620598893	None	None	N
V/F	0.7898	likely_pathogenic	0.8098	pathogenic	-1.143	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/G	0.7463	likely_pathogenic	0.8228	pathogenic	-2.349	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.620598893	None	None	N
V/H	0.9888	likely_pathogenic	0.9928	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/I	0.125	likely_benign	0.1139	benign	-0.503	Destabilizing	0.767	D	0.282	neutral	N	0.479886781	None	None	N
V/K	0.9619	likely_pathogenic	0.9778	pathogenic	-1.661	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/L	0.7479	likely_pathogenic	0.7455	pathogenic	-0.503	Destabilizing	0.981	D	0.643	neutral	D	0.541593268	None	None	N
V/M	0.6825	likely_pathogenic	0.6748	pathogenic	-0.399	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/N	0.9596	likely_pathogenic	0.9729	pathogenic	-1.836	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/P	0.9061	likely_pathogenic	0.9389	pathogenic	-0.923	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/Q	0.9599	likely_pathogenic	0.9739	pathogenic	-1.744	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/R	0.9508	likely_pathogenic	0.9714	pathogenic	-1.409	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/S	0.8861	likely_pathogenic	0.9122	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/T	0.7757	likely_pathogenic	0.797	pathogenic	-2.111	Highly Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/W	0.9927	likely_pathogenic	0.9946	pathogenic	-1.62	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/Y	0.9595	likely_pathogenic	0.9727	pathogenic	-1.213	Destabilizing	1.0	D	0.811	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.