TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23546	70861;70862;70863	chr2:178575496;178575495;178575494	chr2:179440223;179440222;179440221
N2AB	21905	65938;65939;65940	chr2:178575496;178575495;178575494	chr2:179440223;179440222;179440221
N2A	20978	63157;63158;63159	chr2:178575496;178575495;178575494	chr2:179440223;179440222;179440221
N2B	14481	43666;43667;43668	chr2:178575496;178575495;178575494	chr2:179440223;179440222;179440221
Novex-1	14606	44041;44042;44043	chr2:178575496;178575495;178575494	chr2:179440223;179440222;179440221
Novex-2	14673	44242;44243;44244	chr2:178575496;178575495;178575494	chr2:179440223;179440222;179440221
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: Fn3-59
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3521
• 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	0.027	N	0.274	0.094	0.210429274316	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	0.3397	likely_benign	0.2893	benign	-0.166	Destabilizing	0.001	N	0.105	neutral	None	None	None	None	N
K/C	0.7143	likely_pathogenic	0.6719	pathogenic	-0.24	Destabilizing	0.935	D	0.457	neutral	None	None	None	None	N
K/D	0.6256	likely_pathogenic	0.5827	pathogenic	-0.03	Destabilizing	0.001	N	0.169	neutral	None	None	None	None	N
K/E	0.3085	likely_benign	0.2672	benign	-0.021	Destabilizing	0.027	N	0.274	neutral	N	0.487443819	None	None	N
K/F	0.9189	likely_pathogenic	0.8847	pathogenic	-0.373	Destabilizing	0.555	D	0.475	neutral	None	None	None	None	N
K/G	0.3696	ambiguous	0.3022	benign	-0.397	Destabilizing	0.067	N	0.392	neutral	None	None	None	None	N
K/H	0.3575	ambiguous	0.3236	benign	-0.797	Destabilizing	0.555	D	0.407	neutral	None	None	None	None	N
K/I	0.6895	likely_pathogenic	0.6116	pathogenic	0.37	Stabilizing	0.555	D	0.502	neutral	None	None	None	None	N
K/L	0.5718	likely_pathogenic	0.4985	ambiguous	0.37	Stabilizing	0.149	N	0.411	neutral	None	None	None	None	N
K/M	0.4779	ambiguous	0.4104	ambiguous	0.409	Stabilizing	0.741	D	0.4	neutral	N	0.495335616	None	None	N
K/N	0.4844	ambiguous	0.4496	ambiguous	0.155	Stabilizing	0.117	N	0.319	neutral	N	0.491966991	None	None	N
K/P	0.6409	likely_pathogenic	0.5529	ambiguous	0.221	Stabilizing	0.555	D	0.407	neutral	None	None	None	None	N
K/Q	0.1745	likely_benign	0.1539	benign	-0.124	Destabilizing	0.117	N	0.35	neutral	N	0.50774452	None	None	N
K/R	0.0725	likely_benign	0.0693	benign	-0.066	Destabilizing	None	N	0.06	neutral	N	0.448485573	None	None	N
K/S	0.408	ambiguous	0.3522	ambiguous	-0.418	Destabilizing	0.035	N	0.245	neutral	None	None	None	None	N
K/T	0.3346	likely_benign	0.2881	benign	-0.252	Destabilizing	0.117	N	0.351	neutral	N	0.520633673	None	None	N
K/V	0.5801	likely_pathogenic	0.5094	ambiguous	0.221	Stabilizing	0.149	N	0.416	neutral	None	None	None	None	N
K/W	0.8638	likely_pathogenic	0.8207	pathogenic	-0.291	Destabilizing	0.935	D	0.598	neutral	None	None	None	None	N
K/Y	0.7814	likely_pathogenic	0.7284	pathogenic	0.064	Stabilizing	0.555	D	0.458	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.