TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31431	94516;94517;94518	chr2:178547234;178547233;178547232	chr2:179411961;179411960;179411959
N2AB	29790	89593;89594;89595	chr2:178547234;178547233;178547232	chr2:179411961;179411960;179411959
N2A	28863	86812;86813;86814	chr2:178547234;178547233;178547232	chr2:179411961;179411960;179411959
N2B	22366	67321;67322;67323	chr2:178547234;178547233;178547232	chr2:179411961;179411960;179411959
Novex-1	22491	67696;67697;67698	chr2:178547234;178547233;178547232	chr2:179411961;179411960;179411959
Novex-2	22558	67897;67898;67899	chr2:178547234;178547233;178547232	chr2:179411961;179411960;179411959
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: Fn3-117
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6221
• 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	0.986	N	0.549	0.311	0.414798848334	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	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
E/A	0.1181	likely_benign	0.1273	benign	-0.223	Destabilizing	0.826	D	0.457	neutral	N	0.433841407	None	None	N
E/C	0.8203	likely_pathogenic	0.8487	pathogenic	-0.379	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
E/D	0.2304	likely_benign	0.2571	benign	-0.834	Destabilizing	0.986	D	0.557	neutral	N	0.521540537	None	None	N
E/F	0.7908	likely_pathogenic	0.8382	pathogenic	0.349	Stabilizing	0.982	D	0.607	neutral	None	None	None	None	N
E/G	0.2279	likely_benign	0.2671	benign	-0.52	Destabilizing	0.986	D	0.549	neutral	N	0.508360596	None	None	N
E/H	0.6187	likely_pathogenic	0.6839	pathogenic	0.626	Stabilizing	0.999	D	0.581	neutral	None	None	None	None	N
E/I	0.2755	likely_benign	0.3225	benign	0.562	Stabilizing	0.759	D	0.515	neutral	None	None	None	None	N
E/K	0.1416	likely_benign	0.1751	benign	0.042	Stabilizing	0.986	D	0.562	neutral	N	0.423088483	None	None	N
E/L	0.3348	likely_benign	0.3765	ambiguous	0.562	Stabilizing	0.046	N	0.418	neutral	None	None	None	None	N
E/M	0.352	ambiguous	0.3919	ambiguous	0.448	Stabilizing	0.982	D	0.593	neutral	None	None	None	None	N
E/N	0.3768	ambiguous	0.4387	ambiguous	-0.578	Destabilizing	0.997	D	0.59	neutral	None	None	None	None	N
E/P	0.3019	likely_benign	0.3143	benign	0.322	Stabilizing	0.997	D	0.62	neutral	None	None	None	None	N
E/Q	0.1447	likely_benign	0.1615	benign	-0.436	Destabilizing	0.996	D	0.567	neutral	N	0.475768175	None	None	N
E/R	0.283	likely_benign	0.3319	benign	0.466	Stabilizing	0.997	D	0.589	neutral	None	None	None	None	N
E/S	0.2563	likely_benign	0.2974	benign	-0.755	Destabilizing	0.969	D	0.517	neutral	None	None	None	None	N
E/T	0.238	likely_benign	0.2804	benign	-0.489	Destabilizing	0.939	D	0.525	neutral	None	None	None	None	N
E/V	0.1603	likely_benign	0.183	benign	0.322	Stabilizing	0.061	N	0.365	neutral	N	0.480981993	None	None	N
E/W	0.9468	likely_pathogenic	0.9612	pathogenic	0.558	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	N
E/Y	0.682	likely_pathogenic	0.7373	pathogenic	0.619	Stabilizing	0.997	D	0.606	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.