TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19582	58969;58970;58971	chr2:178593464;178593463;178593462	chr2:179458191;179458190;179458189
N2AB	17941	54046;54047;54048	chr2:178593464;178593463;178593462	chr2:179458191;179458190;179458189
N2A	17014	51265;51266;51267	chr2:178593464;178593463;178593462	chr2:179458191;179458190;179458189
N2B	10517	31774;31775;31776	chr2:178593464;178593463;178593462	chr2:179458191;179458190;179458189
Novex-1	10642	32149;32150;32151	chr2:178593464;178593463;178593462	chr2:179458191;179458190;179458189
Novex-2	10709	32350;32351;32352	chr2:178593464;178593463;178593462	chr2:179458191;179458190;179458189
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-30
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1531
• 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
A/T	None	None	1.0	N	0.799	0.441	0.534719010399	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.5606	ambiguous	0.5688	pathogenic	-1.003	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
A/D	0.8349	likely_pathogenic	0.7731	pathogenic	-1.949	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
A/E	0.5837	likely_pathogenic	0.5253	ambiguous	-2.042	Highly Destabilizing	1.0	D	0.837	deleterious	N	0.508736746	None	None	N
A/F	0.667	likely_pathogenic	0.6187	pathogenic	-1.311	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
A/G	0.2678	likely_benign	0.2581	benign	-0.915	Destabilizing	1.0	D	0.663	neutral	N	0.519069547	None	None	N
A/H	0.7152	likely_pathogenic	0.6843	pathogenic	-0.962	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
A/I	0.5434	ambiguous	0.4992	ambiguous	-0.537	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
A/K	0.6199	likely_pathogenic	0.5678	pathogenic	-0.991	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/L	0.5316	ambiguous	0.4749	ambiguous	-0.537	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
A/M	0.4869	ambiguous	0.447	ambiguous	-0.344	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/N	0.6766	likely_pathogenic	0.6317	pathogenic	-0.834	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
A/P	0.2348	likely_benign	0.2225	benign	-0.58	Destabilizing	1.0	D	0.85	deleterious	N	0.448123	None	None	N
A/Q	0.465	ambiguous	0.4502	ambiguous	-1.184	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/R	0.5411	ambiguous	0.4806	ambiguous	-0.519	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
A/S	0.1501	likely_benign	0.1433	benign	-0.978	Destabilizing	1.0	D	0.669	neutral	N	0.480428274	None	None	N
A/T	0.2552	likely_benign	0.2204	benign	-1.012	Destabilizing	1.0	D	0.799	deleterious	N	0.500711803	None	None	N
A/V	0.3374	likely_benign	0.2875	benign	-0.58	Destabilizing	1.0	D	0.703	prob.neutral	N	0.498901377	None	None	N
A/W	0.9397	likely_pathogenic	0.926	pathogenic	-1.532	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/Y	0.7682	likely_pathogenic	0.7371	pathogenic	-1.142	Destabilizing	1.0	D	0.903	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.