TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24739	74440;74441;74442	chr2:178571917;178571916;178571915	chr2:179436644;179436643;179436642
N2AB	23098	69517;69518;69519	chr2:178571917;178571916;178571915	chr2:179436644;179436643;179436642
N2A	22171	66736;66737;66738	chr2:178571917;178571916;178571915	chr2:179436644;179436643;179436642
N2B	15674	47245;47246;47247	chr2:178571917;178571916;178571915	chr2:179436644;179436643;179436642
Novex-1	15799	47620;47621;47622	chr2:178571917;178571916;178571915	chr2:179436644;179436643;179436642
Novex-2	15866	47821;47822;47823	chr2:178571917;178571916;178571915	chr2:179436644;179436643;179436642
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-133
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1256
• 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
F/L	None	None	0.309	N	0.583	0.332	0.298056030225	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	2.28749E-05	None	0	0	None	0	0	0	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
F/A	0.8596	likely_pathogenic	0.8691	pathogenic	-3.265	Highly Destabilizing	0.59	D	0.717	prob.delet.	None	None	None	None	N
F/C	0.3614	ambiguous	0.3798	ambiguous	-1.977	Destabilizing	0.994	D	0.748	deleterious	N	0.504557507	None	None	N
F/D	0.9927	likely_pathogenic	0.993	pathogenic	-3.751	Highly Destabilizing	0.984	D	0.815	deleterious	None	None	None	None	N
F/E	0.9909	likely_pathogenic	0.9917	pathogenic	-3.544	Highly Destabilizing	0.953	D	0.798	deleterious	None	None	None	None	N
F/G	0.9589	likely_pathogenic	0.9588	pathogenic	-3.687	Highly Destabilizing	0.854	D	0.781	deleterious	None	None	None	None	N
F/H	0.8308	likely_pathogenic	0.8347	pathogenic	-2.283	Highly Destabilizing	0.91	D	0.745	deleterious	None	None	None	None	N
F/I	0.2836	likely_benign	0.3445	ambiguous	-1.859	Destabilizing	0.521	D	0.652	neutral	N	0.440181095	None	None	N
F/K	0.9799	likely_pathogenic	0.982	pathogenic	-2.222	Highly Destabilizing	0.953	D	0.802	deleterious	None	None	None	None	N
F/L	0.9237	likely_pathogenic	0.9394	pathogenic	-1.859	Destabilizing	0.309	N	0.583	neutral	N	0.488977906	None	None	N
F/M	0.6846	likely_pathogenic	0.7202	pathogenic	-1.601	Destabilizing	0.953	D	0.679	prob.neutral	None	None	None	None	N
F/N	0.9569	likely_pathogenic	0.9594	pathogenic	-2.721	Highly Destabilizing	0.984	D	0.813	deleterious	None	None	None	None	N
F/P	0.9977	likely_pathogenic	0.998	pathogenic	-2.343	Highly Destabilizing	0.984	D	0.813	deleterious	None	None	None	None	N
F/Q	0.9637	likely_pathogenic	0.9661	pathogenic	-2.688	Highly Destabilizing	0.984	D	0.814	deleterious	None	None	None	None	N
F/R	0.9502	likely_pathogenic	0.9538	pathogenic	-1.715	Destabilizing	0.953	D	0.815	deleterious	None	None	None	None	N
F/S	0.8477	likely_pathogenic	0.8535	pathogenic	-3.278	Highly Destabilizing	0.815	D	0.778	deleterious	D	0.534635625	None	None	N
F/T	0.8852	likely_pathogenic	0.8988	pathogenic	-2.964	Highly Destabilizing	0.742	D	0.759	deleterious	None	None	None	None	N
F/V	0.2651	likely_benign	0.3085	benign	-2.343	Highly Destabilizing	0.007	N	0.425	neutral	N	0.396883316	None	None	N
F/W	0.6309	likely_pathogenic	0.6206	pathogenic	-0.683	Destabilizing	0.953	D	0.651	neutral	None	None	None	None	N
F/Y	0.1634	likely_benign	0.1507	benign	-1.175	Destabilizing	0.012	N	0.223	neutral	N	0.460735299	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.