TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22872	68839;68840;68841	chr2:178577812;178577811;178577810	chr2:179442539;179442538;179442537
N2AB	21231	63916;63917;63918	chr2:178577812;178577811;178577810	chr2:179442539;179442538;179442537
N2A	20304	61135;61136;61137	chr2:178577812;178577811;178577810	chr2:179442539;179442538;179442537
N2B	13807	41644;41645;41646	chr2:178577812;178577811;178577810	chr2:179442539;179442538;179442537
Novex-1	13932	42019;42020;42021	chr2:178577812;178577811;178577810	chr2:179442539;179442538;179442537
Novex-2	13999	42220;42221;42222	chr2:178577812;178577811;178577810	chr2:179442539;179442538;179442537
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-54
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5449
• 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
K/E	None	None	0.822	N	0.58	0.258	0.28058544554	gnomAD-4.0.0	1.59481E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43802E-05	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
K/A	0.4175	ambiguous	0.4954	ambiguous	-0.105	Destabilizing	0.86	D	0.618	neutral	None	None	None	None	N
K/C	0.6817	likely_pathogenic	0.748	pathogenic	-0.136	Destabilizing	0.998	D	0.736	prob.delet.	None	None	None	None	N
K/D	0.7645	likely_pathogenic	0.8258	pathogenic	0.087	Stabilizing	0.978	D	0.601	neutral	None	None	None	None	N
K/E	0.3407	ambiguous	0.401	ambiguous	0.104	Stabilizing	0.822	D	0.58	neutral	N	0.499738325	None	None	N
K/F	0.8071	likely_pathogenic	0.8597	pathogenic	-0.246	Destabilizing	0.956	D	0.733	prob.delet.	None	None	None	None	N
K/G	0.5976	likely_pathogenic	0.6741	pathogenic	-0.336	Destabilizing	0.86	D	0.597	neutral	None	None	None	None	N
K/H	0.3299	likely_benign	0.3708	ambiguous	-0.667	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
K/I	0.392	ambiguous	0.4554	ambiguous	0.433	Stabilizing	0.915	D	0.719	prob.delet.	None	None	None	None	N
K/L	0.3891	ambiguous	0.4468	ambiguous	0.433	Stabilizing	0.754	D	0.624	neutral	None	None	None	None	N
K/M	0.3104	likely_benign	0.3641	ambiguous	0.331	Stabilizing	0.489	N	0.514	neutral	N	0.472814043	None	None	N
K/N	0.615	likely_pathogenic	0.6916	pathogenic	0.219	Stabilizing	0.97	D	0.576	neutral	N	0.476977872	None	None	N
K/P	0.4892	ambiguous	0.5491	ambiguous	0.283	Stabilizing	0.019	N	0.365	neutral	None	None	None	None	N
K/Q	0.1591	likely_benign	0.1778	benign	0.026	Stabilizing	0.97	D	0.607	neutral	N	0.516537362	None	None	N
K/R	0.0804	likely_benign	0.0822	benign	-0.079	Destabilizing	0.904	D	0.548	neutral	N	0.465513895	None	None	N
K/S	0.552	ambiguous	0.6262	pathogenic	-0.318	Destabilizing	0.86	D	0.571	neutral	None	None	None	None	N
K/T	0.2642	likely_benign	0.3148	benign	-0.142	Destabilizing	0.942	D	0.597	neutral	N	0.502896061	None	None	N
K/V	0.3556	ambiguous	0.4104	ambiguous	0.283	Stabilizing	0.754	D	0.607	neutral	None	None	None	None	N
K/W	0.7986	likely_pathogenic	0.8485	pathogenic	-0.216	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
K/Y	0.6954	likely_pathogenic	0.7608	pathogenic	0.124	Stabilizing	0.993	D	0.715	prob.delet.	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.