TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30897	92914;92915;92916	chr2:178548937;178548936;178548935	chr2:179413664;179413663;179413662
N2AB	29256	87991;87992;87993	chr2:178548937;178548936;178548935	chr2:179413664;179413663;179413662
N2A	28329	85210;85211;85212	chr2:178548937;178548936;178548935	chr2:179413664;179413663;179413662
N2B	21832	65719;65720;65721	chr2:178548937;178548936;178548935	chr2:179413664;179413663;179413662
Novex-1	21957	66094;66095;66096	chr2:178548937;178548936;178548935	chr2:179413664;179413663;179413662
Novex-2	22024	66295;66296;66297	chr2:178548937;178548936;178548935	chr2:179413664;179413663;179413662
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-113
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1037
• 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
S/G	None	None	0.989	N	0.634	0.331	0.257292322809	gnomAD-4.0.0	1.59107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
S/A	0.0966	likely_benign	0.095	benign	-1.03	Destabilizing	0.96	D	0.582	neutral	None	None	None	None	N
S/C	0.067	likely_benign	0.0712	benign	-1.059	Destabilizing	0.241	N	0.581	neutral	N	0.464185744	None	None	N
S/D	0.7338	likely_pathogenic	0.7091	pathogenic	-2.116	Highly Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
S/E	0.7719	likely_pathogenic	0.7348	pathogenic	-1.899	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
S/F	0.2297	likely_benign	0.2492	benign	-0.718	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
S/G	0.128	likely_benign	0.1288	benign	-1.416	Destabilizing	0.989	D	0.634	neutral	N	0.494904316	None	None	N
S/H	0.4531	ambiguous	0.4201	ambiguous	-1.66	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
S/I	0.2635	likely_benign	0.2613	benign	-0.042	Destabilizing	0.997	D	0.812	deleterious	N	0.503280063	None	None	N
S/K	0.852	likely_pathogenic	0.812	pathogenic	-0.618	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
S/L	0.1525	likely_benign	0.155	benign	-0.042	Destabilizing	0.983	D	0.767	deleterious	None	None	None	None	N
S/M	0.2259	likely_benign	0.2356	benign	-0.291	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
S/N	0.2727	likely_benign	0.2495	benign	-1.427	Destabilizing	0.999	D	0.678	prob.neutral	N	0.486003546	None	None	N
S/P	0.9752	likely_pathogenic	0.9783	pathogenic	-0.339	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
S/Q	0.6172	likely_pathogenic	0.5644	pathogenic	-1.124	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
S/R	0.6991	likely_pathogenic	0.6249	pathogenic	-0.964	Destabilizing	0.999	D	0.791	deleterious	N	0.447482708	None	None	N
S/T	0.1039	likely_benign	0.1019	benign	-1.012	Destabilizing	0.989	D	0.623	neutral	N	0.491273558	None	None	N
S/V	0.2559	likely_benign	0.2535	benign	-0.339	Destabilizing	0.995	D	0.793	deleterious	None	None	None	None	N
S/W	0.3784	ambiguous	0.3807	ambiguous	-1.062	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
S/Y	0.2392	likely_benign	0.2405	benign	-0.615	Destabilizing	0.999	D	0.827	deleterious	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.