TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17615	53068;53069;53070	chr2:178607944;178607943;178607942	chr2:179472671;179472670;179472669
N2AB	15974	48145;48146;48147	chr2:178607944;178607943;178607942	chr2:179472671;179472670;179472669
N2A	15047	45364;45365;45366	chr2:178607944;178607943;178607942	chr2:179472671;179472670;179472669
N2B	8550	25873;25874;25875	chr2:178607944;178607943;178607942	chr2:179472671;179472670;179472669
Novex-1	8675	26248;26249;26250	chr2:178607944;178607943;178607942	chr2:179472671;179472670;179472669
Novex-2	8742	26449;26450;26451	chr2:178607944;178607943;178607942	chr2:179472671;179472670;179472669
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: Fn3-16
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.7024
• 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
E/G	None	None	0.961	N	0.435	0.442	0.415438038341	gnomAD-4.0.0	1.59276E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86131E-06	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
E/A	0.1853	likely_benign	0.1654	benign	-0.166	Destabilizing	0.98	D	0.413	neutral	N	0.488121396	None	None	N
E/C	0.8597	likely_pathogenic	0.8249	pathogenic	-0.079	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
E/D	0.1371	likely_benign	0.1287	benign	-0.192	Destabilizing	0.011	N	0.218	neutral	N	0.41354628	None	None	N
E/F	0.7692	likely_pathogenic	0.7299	pathogenic	-0.176	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
E/G	0.2167	likely_benign	0.1915	benign	-0.305	Destabilizing	0.961	D	0.435	neutral	N	0.474594739	None	None	N
E/H	0.4954	ambiguous	0.4524	ambiguous	0.304	Stabilizing	0.999	D	0.389	neutral	None	None	None	None	N
E/I	0.3341	likely_benign	0.3108	benign	0.15	Stabilizing	0.999	D	0.542	neutral	None	None	None	None	N
E/K	0.1681	likely_benign	0.1405	benign	0.383	Stabilizing	0.961	D	0.404	neutral	N	0.440367522	None	None	N
E/L	0.4264	ambiguous	0.4047	ambiguous	0.15	Stabilizing	0.996	D	0.545	neutral	None	None	None	None	N
E/M	0.4898	ambiguous	0.4467	ambiguous	0.068	Stabilizing	1.0	D	0.532	neutral	None	None	None	None	N
E/N	0.2894	likely_benign	0.256	benign	0.198	Stabilizing	0.97	D	0.387	neutral	None	None	None	None	N
E/P	0.845	likely_pathogenic	0.8387	pathogenic	0.063	Stabilizing	0.999	D	0.407	neutral	None	None	None	None	N
E/Q	0.1523	likely_benign	0.1381	benign	0.208	Stabilizing	0.98	D	0.363	neutral	N	0.474210737	None	None	N
E/R	0.3029	likely_benign	0.2655	benign	0.607	Stabilizing	0.996	D	0.393	neutral	None	None	None	None	N
E/S	0.257	likely_benign	0.2287	benign	0.018	Stabilizing	0.97	D	0.401	neutral	None	None	None	None	N
E/T	0.2227	likely_benign	0.1975	benign	0.134	Stabilizing	0.985	D	0.378	neutral	None	None	None	None	N
E/V	0.2041	likely_benign	0.1891	benign	0.063	Stabilizing	0.998	D	0.466	neutral	N	0.485755882	None	None	N
E/W	0.9192	likely_pathogenic	0.8978	pathogenic	-0.095	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
E/Y	0.6408	likely_pathogenic	0.5995	pathogenic	0.055	Stabilizing	0.999	D	0.494	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.