TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24834	74725;74726;74727	chr2:178571632;178571631;178571630	chr2:179436359;179436358;179436357
N2AB	23193	69802;69803;69804	chr2:178571632;178571631;178571630	chr2:179436359;179436358;179436357
N2A	22266	67021;67022;67023	chr2:178571632;178571631;178571630	chr2:179436359;179436358;179436357
N2B	15769	47530;47531;47532	chr2:178571632;178571631;178571630	chr2:179436359;179436358;179436357
Novex-1	15894	47905;47906;47907	chr2:178571632;178571631;178571630	chr2:179436359;179436358;179436357
Novex-2	15961	48106;48107;48108	chr2:178571632;178571631;178571630	chr2:179436359;179436358;179436357
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: Fn3-68
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.5341
• 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/R	None	None	0.684	N	0.375	0.129	0.270889551736	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-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	0.1212	likely_benign	0.12	benign	0.052	Stabilizing	0.543	D	0.341	neutral	None	None	None	None	N
K/C	0.4756	ambiguous	0.447	ambiguous	-0.4	Destabilizing	0.996	D	0.289	neutral	None	None	None	None	N
K/D	0.2414	likely_benign	0.2368	benign	-0.208	Destabilizing	0.009	N	0.19	neutral	None	None	None	None	N
K/E	0.0771	likely_benign	0.0738	benign	-0.216	Destabilizing	0.001	N	0.088	neutral	N	0.412314129	None	None	N
K/F	0.5519	ambiguous	0.5108	ambiguous	-0.245	Destabilizing	0.984	D	0.297	neutral	None	None	None	None	N
K/G	0.2466	likely_benign	0.234	benign	-0.094	Destabilizing	0.742	D	0.393	neutral	None	None	None	None	N
K/H	0.2424	likely_benign	0.2334	benign	-0.201	Destabilizing	0.953	D	0.318	neutral	None	None	None	None	N
K/I	0.1359	likely_benign	0.1315	benign	0.351	Stabilizing	0.953	D	0.336	neutral	None	None	None	None	N
K/L	0.1493	likely_benign	0.1411	benign	0.351	Stabilizing	0.742	D	0.413	neutral	None	None	None	None	N
K/M	0.1306	likely_benign	0.1255	benign	-0.021	Destabilizing	0.994	D	0.315	neutral	N	0.475157901	None	None	N
K/N	0.2131	likely_benign	0.2051	benign	0.063	Stabilizing	0.521	D	0.339	neutral	N	0.509035386	None	None	N
K/P	0.4111	ambiguous	0.3901	ambiguous	0.276	Stabilizing	0.953	D	0.369	neutral	None	None	None	None	N
K/Q	0.0901	likely_benign	0.0872	benign	-0.085	Destabilizing	0.078	N	0.207	neutral	N	0.468188841	None	None	N
K/R	0.0859	likely_benign	0.0833	benign	-0.062	Destabilizing	0.684	D	0.375	neutral	N	0.483926298	None	None	N
K/S	0.1805	likely_benign	0.1708	benign	-0.32	Destabilizing	0.543	D	0.329	neutral	None	None	None	None	N
K/T	0.0889	likely_benign	0.0881	benign	-0.204	Destabilizing	0.684	D	0.376	neutral	N	0.460588078	None	None	N
K/V	0.1128	likely_benign	0.1108	benign	0.276	Stabilizing	0.854	D	0.374	neutral	None	None	None	None	N
K/W	0.6829	likely_pathogenic	0.6532	pathogenic	-0.332	Destabilizing	0.996	D	0.361	neutral	None	None	None	None	N
K/Y	0.4451	ambiguous	0.4277	ambiguous	0.023	Stabilizing	0.984	D	0.335	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.