TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35298	106117;106118;106119	chr2:178530723;178530722;178530721	chr2:179395450;179395449;179395448
N2AB	33657	101194;101195;101196	chr2:178530723;178530722;178530721	chr2:179395450;179395449;179395448
N2A	32730	98413;98414;98415	chr2:178530723;178530722;178530721	chr2:179395450;179395449;179395448
N2B	26233	78922;78923;78924	chr2:178530723;178530722;178530721	chr2:179395450;179395449;179395448
Novex-1	26358	79297;79298;79299	chr2:178530723;178530722;178530721	chr2:179395450;179395449;179395448
Novex-2	26425	79498;79499;79500	chr2:178530723;178530722;178530721	chr2:179395450;179395449;179395448
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-165
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.7585
• 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	rs1038411721	None	None	N	0.137	0.086	0.126345400529	gnomAD-4.0.0	1.59097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85758E-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	0.2682	likely_benign	0.2354	benign	-0.026	Destabilizing	None	N	0.183	neutral	None	None	None	None	N
K/C	0.7918	likely_pathogenic	0.7553	pathogenic	-0.526	Destabilizing	0.448	N	0.211	neutral	None	None	None	None	N
K/D	0.3171	likely_benign	0.2823	benign	-0.268	Destabilizing	None	N	0.173	neutral	None	None	None	None	N
K/E	0.0945	likely_benign	0.0849	benign	-0.284	Destabilizing	None	N	0.137	neutral	N	0.442652026	None	None	N
K/F	0.8319	likely_pathogenic	0.7865	pathogenic	-0.394	Destabilizing	0.177	N	0.259	neutral	None	None	None	None	N
K/G	0.2472	likely_benign	0.2154	benign	-0.141	Destabilizing	None	N	0.171	neutral	None	None	None	None	N
K/H	0.3896	ambiguous	0.3666	ambiguous	-0.235	Destabilizing	0.177	N	0.236	neutral	None	None	None	None	N
K/I	0.5209	ambiguous	0.4502	ambiguous	0.192	Stabilizing	0.022	N	0.329	neutral	N	0.449409966	None	None	N
K/L	0.4095	ambiguous	0.3534	ambiguous	0.192	Stabilizing	0.012	N	0.308	neutral	None	None	None	None	N
K/M	0.2868	likely_benign	0.2473	benign	-0.142	Destabilizing	0.396	N	0.235	neutral	None	None	None	None	N
K/N	0.2563	likely_benign	0.2326	benign	-0.079	Destabilizing	0.005	N	0.281	neutral	N	0.420679243	None	None	N
K/P	0.5031	ambiguous	0.4528	ambiguous	0.142	Stabilizing	0.058	N	0.341	neutral	None	None	None	None	N
K/Q	0.1327	likely_benign	0.1242	benign	-0.21	Destabilizing	0.011	N	0.303	neutral	N	0.494003566	None	None	N
K/R	0.0957	likely_benign	0.0897	benign	-0.161	Destabilizing	None	N	0.22	neutral	N	0.475591163	None	None	N
K/S	0.2722	likely_benign	0.2435	benign	-0.445	Destabilizing	0.006	N	0.248	neutral	None	None	None	None	N
K/T	0.1773	likely_benign	0.1575	benign	-0.346	Destabilizing	0.009	N	0.318	neutral	N	0.461680504	None	None	N
K/V	0.4332	ambiguous	0.3664	ambiguous	0.142	Stabilizing	0.015	N	0.327	neutral	None	None	None	None	N
K/W	0.8284	likely_pathogenic	0.7848	pathogenic	-0.5	Destabilizing	0.712	D	0.209	neutral	None	None	None	None	N
K/Y	0.694	likely_pathogenic	0.6418	pathogenic	-0.148	Destabilizing	0.396	N	0.275	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.