TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29187	87784;87785;87786	chr2:178557795;178557794;178557793	chr2:179422522;179422521;179422520
N2AB	27546	82861;82862;82863	chr2:178557795;178557794;178557793	chr2:179422522;179422521;179422520
N2A	26619	80080;80081;80082	chr2:178557795;178557794;178557793	chr2:179422522;179422521;179422520
N2B	20122	60589;60590;60591	chr2:178557795;178557794;178557793	chr2:179422522;179422521;179422520
Novex-1	20247	60964;60965;60966	chr2:178557795;178557794;178557793	chr2:179422522;179422521;179422520
Novex-2	20314	61165;61166;61167	chr2:178557795;178557794;178557793	chr2:179422522;179422521;179422520
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-100
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.3888
• 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
E/D	None	None	0.104	N	0.209	0.069	0.112648838833	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs1060500586	0.233	0.994	N	0.582	0.377	0.357519025918	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs1060500586	0.233	0.994	N	0.582	0.377	0.357519025918	gnomAD-4.0.0	6.15749E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.04345E-04	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
E/A	0.2412	likely_benign	0.3095	benign	-0.631	Destabilizing	0.994	D	0.653	neutral	N	0.450163228	None	None	I
E/C	0.9331	likely_pathogenic	0.951	pathogenic	-0.165	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
E/D	0.2715	likely_benign	0.3469	ambiguous	-0.526	Destabilizing	0.104	N	0.209	neutral	N	0.439831591	None	None	I
E/F	0.9404	likely_pathogenic	0.9596	pathogenic	-0.33	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/G	0.4122	ambiguous	0.5169	ambiguous	-0.878	Destabilizing	0.994	D	0.638	neutral	N	0.502304202	None	None	I
E/H	0.7762	likely_pathogenic	0.8448	pathogenic	-0.227	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
E/I	0.5123	ambiguous	0.5896	pathogenic	0.007	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
E/K	0.3357	likely_benign	0.4308	ambiguous	0.175	Stabilizing	0.994	D	0.582	neutral	N	0.425208855	None	None	I
E/L	0.5935	likely_pathogenic	0.6652	pathogenic	0.007	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
E/M	0.5867	likely_pathogenic	0.6621	pathogenic	0.208	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/N	0.4469	ambiguous	0.5701	pathogenic	-0.32	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	I
E/P	0.5404	ambiguous	0.6079	pathogenic	-0.185	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
E/Q	0.2583	likely_benign	0.3238	benign	-0.253	Destabilizing	0.998	D	0.643	neutral	N	0.456550483	None	None	I
E/R	0.5578	ambiguous	0.6532	pathogenic	0.397	Stabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
E/S	0.3738	ambiguous	0.4852	ambiguous	-0.479	Destabilizing	0.992	D	0.594	neutral	None	None	None	None	I
E/T	0.3293	likely_benign	0.4207	ambiguous	-0.269	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	I
E/V	0.2801	likely_benign	0.3304	benign	-0.185	Destabilizing	0.999	D	0.761	deleterious	N	0.402409353	None	None	I
E/W	0.9837	likely_pathogenic	0.9897	pathogenic	-0.093	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/Y	0.8797	likely_pathogenic	0.9202	pathogenic	-0.068	Destabilizing	1.0	D	0.753	deleterious	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.