TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23228	69907;69908;69909	chr2:178576562;178576561;178576560	chr2:179441289;179441288;179441287
N2AB	21587	64984;64985;64986	chr2:178576562;178576561;178576560	chr2:179441289;179441288;179441287
N2A	20660	62203;62204;62205	chr2:178576562;178576561;178576560	chr2:179441289;179441288;179441287
N2B	14163	42712;42713;42714	chr2:178576562;178576561;178576560	chr2:179441289;179441288;179441287
Novex-1	14288	43087;43088;43089	chr2:178576562;178576561;178576560	chr2:179441289;179441288;179441287
Novex-2	14355	43288;43289;43290	chr2:178576562;178576561;178576560	chr2:179441289;179441288;179441287
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-56
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.2746
• 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
A/S	None	None	0.001	N	0.283	0.051	0.0954503805726	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
A/C	0.3788	ambiguous	0.3368	benign	-1.009	Destabilizing	0.778	D	0.493	neutral	None	None	None	None	N
A/D	0.3566	ambiguous	0.3327	benign	-1.517	Destabilizing	0.09	N	0.528	neutral	N	0.466578937	None	None	N
A/E	0.264	likely_benign	0.2493	benign	-1.549	Destabilizing	0.116	N	0.503	neutral	None	None	None	None	N
A/F	0.3488	ambiguous	0.3152	benign	-1.224	Destabilizing	0.314	N	0.615	neutral	None	None	None	None	N
A/G	0.1368	likely_benign	0.1268	benign	-1.363	Destabilizing	0.02	N	0.296	neutral	N	0.462958086	None	None	N
A/H	0.4989	ambiguous	0.4554	ambiguous	-1.468	Destabilizing	0.739	D	0.613	neutral	None	None	None	None	N
A/I	0.146	likely_benign	0.1325	benign	-0.57	Destabilizing	0.022	N	0.543	neutral	None	None	None	None	N
A/K	0.4236	ambiguous	0.3799	ambiguous	-1.23	Destabilizing	0.116	N	0.53	neutral	None	None	None	None	N
A/L	0.1571	likely_benign	0.1427	benign	-0.57	Destabilizing	0.026	N	0.357	neutral	None	None	None	None	N
A/M	0.1789	likely_benign	0.1674	benign	-0.443	Destabilizing	0.314	N	0.483	neutral	None	None	None	None	N
A/N	0.2573	likely_benign	0.2244	benign	-0.959	Destabilizing	0.116	N	0.575	neutral	None	None	None	None	N
A/P	0.0797	likely_benign	0.0718	benign	-0.711	Destabilizing	None	N	0.366	neutral	N	0.35997558	None	None	N
A/Q	0.3392	likely_benign	0.3152	benign	-1.164	Destabilizing	0.482	N	0.57	neutral	None	None	None	None	N
A/R	0.4181	ambiguous	0.3865	ambiguous	-0.854	Destabilizing	0.314	N	0.574	neutral	None	None	None	None	N
A/S	0.1003	likely_benign	0.0959	benign	-1.302	Destabilizing	0.001	N	0.283	neutral	N	0.453560532	None	None	N
A/T	0.0913	likely_benign	0.0854	benign	-1.25	Destabilizing	None	N	0.247	neutral	N	0.432915901	None	None	N
A/V	0.0906	likely_benign	0.0849	benign	-0.711	Destabilizing	None	N	0.219	neutral	N	0.434993414	None	None	N
A/W	0.7298	likely_pathogenic	0.6829	pathogenic	-1.532	Destabilizing	0.914	D	0.717	prob.delet.	None	None	None	None	N
A/Y	0.4774	ambiguous	0.4214	ambiguous	-1.156	Destabilizing	0.482	N	0.609	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.