TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30993	93202;93203;93204	chr2:178548649;178548648;178548647	chr2:179413376;179413375;179413374
N2AB	29352	88279;88280;88281	chr2:178548649;178548648;178548647	chr2:179413376;179413375;179413374
N2A	28425	85498;85499;85500	chr2:178548649;178548648;178548647	chr2:179413376;179413375;179413374
N2B	21928	66007;66008;66009	chr2:178548649;178548648;178548647	chr2:179413376;179413375;179413374
Novex-1	22053	66382;66383;66384	chr2:178548649;178548648;178548647	chr2:179413376;179413375;179413374
Novex-2	22120	66583;66584;66585	chr2:178548649;178548648;178548647	chr2:179413376;179413375;179413374
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-150
• Domain position: 67
• Structural Position: 153
• Q(SASA): 0.6237
• 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/N	rs754893239	None	0.884	D	0.371	0.231	0.215869574891	gnomAD-4.0.0	1.36836E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79889E-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	0.9065	likely_pathogenic	0.9038	pathogenic	-0.381	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
K/C	0.9264	likely_pathogenic	0.9237	pathogenic	-0.325	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/D	0.9646	likely_pathogenic	0.9605	pathogenic	0.095	Stabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
K/E	0.8305	likely_pathogenic	0.822	pathogenic	0.165	Stabilizing	0.996	D	0.583	neutral	N	0.518994169	None	None	N
K/F	0.9715	likely_pathogenic	0.9674	pathogenic	-0.237	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
K/G	0.9469	likely_pathogenic	0.9406	pathogenic	-0.7	Destabilizing	0.997	D	0.628	neutral	None	None	None	None	N
K/H	0.6757	likely_pathogenic	0.6618	pathogenic	-1.072	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
K/I	0.7423	likely_pathogenic	0.7238	pathogenic	0.418	Stabilizing	1.0	D	0.707	prob.neutral	D	0.525325495	None	None	N
K/L	0.7945	likely_pathogenic	0.7848	pathogenic	0.418	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/M	0.68	likely_pathogenic	0.6659	pathogenic	0.319	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/N	0.9068	likely_pathogenic	0.8991	pathogenic	-0.089	Destabilizing	0.884	D	0.371	neutral	D	0.523170624	None	None	N
K/P	0.9638	likely_pathogenic	0.9635	pathogenic	0.182	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/Q	0.5073	ambiguous	0.5006	ambiguous	-0.217	Destabilizing	0.999	D	0.658	neutral	D	0.529923238	None	None	N
K/R	0.1191	likely_benign	0.1209	benign	-0.394	Destabilizing	0.998	D	0.581	neutral	N	0.503064711	None	None	N
K/S	0.9226	likely_pathogenic	0.9161	pathogenic	-0.722	Destabilizing	0.997	D	0.597	neutral	None	None	None	None	N
K/T	0.6938	likely_pathogenic	0.6786	pathogenic	-0.46	Destabilizing	0.999	D	0.69	prob.neutral	N	0.504776865	None	None	N
K/V	0.7433	likely_pathogenic	0.73	pathogenic	0.182	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/W	0.9516	likely_pathogenic	0.952	pathogenic	-0.128	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/Y	0.9115	likely_pathogenic	0.9039	pathogenic	0.169	Stabilizing	1.0	D	0.701	prob.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.