TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18456	55591;55592;55593	chr2:178601724;178601723;178601722	chr2:179466451;179466450;179466449
N2AB	16815	50668;50669;50670	chr2:178601724;178601723;178601722	chr2:179466451;179466450;179466449
N2A	15888	47887;47888;47889	chr2:178601724;178601723;178601722	chr2:179466451;179466450;179466449
N2B	9391	28396;28397;28398	chr2:178601724;178601723;178601722	chr2:179466451;179466450;179466449
Novex-1	9516	28771;28772;28773	chr2:178601724;178601723;178601722	chr2:179466451;179466450;179466449
Novex-2	9583	28972;28973;28974	chr2:178601724;178601723;178601722	chr2:179466451;179466450;179466449
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-115
• Domain position: 75
• Structural Position: 153
• Q(SASA): 0.728
• 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/I	None	None	0.896	N	0.581	0.392	0.591556180789	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
K/A	0.647	likely_pathogenic	0.6706	pathogenic	-0.797	Destabilizing	0.4	N	0.514	neutral	None	None	None	None	N
K/C	0.721	likely_pathogenic	0.6904	pathogenic	-0.849	Destabilizing	0.992	D	0.572	neutral	None	None	None	None	N
K/D	0.848	likely_pathogenic	0.8669	pathogenic	-0.549	Destabilizing	0.617	D	0.533	neutral	None	None	None	None	N
K/E	0.5395	ambiguous	0.5892	pathogenic	-0.436	Destabilizing	0.334	N	0.565	neutral	N	0.478590341	None	None	N
K/F	0.8076	likely_pathogenic	0.8105	pathogenic	-0.626	Destabilizing	0.972	D	0.574	neutral	None	None	None	None	N
K/G	0.7747	likely_pathogenic	0.7912	pathogenic	-1.161	Destabilizing	0.617	D	0.529	neutral	None	None	None	None	N
K/H	0.3717	ambiguous	0.3581	ambiguous	-1.613	Destabilizing	0.92	D	0.555	neutral	None	None	None	None	N
K/I	0.3727	ambiguous	0.4015	ambiguous	0.153	Stabilizing	0.896	D	0.581	neutral	N	0.474147313	None	None	N
K/L	0.4744	ambiguous	0.4939	ambiguous	0.153	Stabilizing	0.617	D	0.529	neutral	None	None	None	None	N
K/M	0.3339	likely_benign	0.3627	ambiguous	0.202	Stabilizing	0.972	D	0.547	neutral	None	None	None	None	N
K/N	0.6417	likely_pathogenic	0.6605	pathogenic	-0.702	Destabilizing	0.549	D	0.505	neutral	N	0.496504098	None	None	N
K/P	0.9239	likely_pathogenic	0.9406	pathogenic	-0.134	Destabilizing	0.92	D	0.554	neutral	None	None	None	None	N
K/Q	0.2487	likely_benign	0.2619	benign	-0.832	Destabilizing	0.549	D	0.544	neutral	N	0.518879526	None	None	N
K/R	0.0816	likely_benign	0.0819	benign	-0.736	Destabilizing	0.001	N	0.135	neutral	N	0.424142568	None	None	N
K/S	0.6935	likely_pathogenic	0.7016	pathogenic	-1.367	Destabilizing	0.617	D	0.528	neutral	None	None	None	None	N
K/T	0.3113	likely_benign	0.3273	benign	-1.044	Destabilizing	0.549	D	0.513	neutral	N	0.477571621	None	None	N
K/V	0.39	ambiguous	0.4108	ambiguous	-0.134	Destabilizing	0.85	D	0.541	neutral	None	None	None	None	N
K/W	0.7601	likely_pathogenic	0.7328	pathogenic	-0.494	Destabilizing	0.992	D	0.603	neutral	None	None	None	None	N
K/Y	0.6527	likely_pathogenic	0.6557	pathogenic	-0.159	Destabilizing	0.972	D	0.583	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.