TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5223	15892;15893;15894	chr2:178733722;178733721;178733720	chr2:179598449;179598448;179598447
N2AB	4906	14941;14942;14943	chr2:178733722;178733721;178733720	chr2:179598449;179598448;179598447
N2A	3979	12160;12161;12162	chr2:178733722;178733721;178733720	chr2:179598449;179598448;179598447
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-35
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1043
• 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	rs749315462	None	0.698	N	0.637	0.176	0.300110245524	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
A/T	rs749315462	-1.078	0.032	D	0.484	0.219	0.341934017632	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65563E-04

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	0.6649	likely_pathogenic	0.6823	pathogenic	-0.559	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
A/D	0.9762	likely_pathogenic	0.9843	pathogenic	-1.26	Destabilizing	0.956	D	0.769	deleterious	None	None	None	None	N
A/E	0.9603	likely_pathogenic	0.9722	pathogenic	-1.114	Destabilizing	0.942	D	0.727	prob.delet.	D	0.537784147	None	None	N
A/F	0.8264	likely_pathogenic	0.8463	pathogenic	-0.498	Destabilizing	0.978	D	0.773	deleterious	None	None	None	None	N
A/G	0.2492	likely_benign	0.2752	benign	-1.147	Destabilizing	0.822	D	0.641	neutral	D	0.542407635	None	None	N
A/H	0.9715	likely_pathogenic	0.9765	pathogenic	-1.559	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
A/I	0.5749	likely_pathogenic	0.6404	pathogenic	0.443	Stabilizing	0.754	D	0.705	prob.neutral	None	None	None	None	N
A/K	0.9853	likely_pathogenic	0.9896	pathogenic	-0.703	Destabilizing	0.956	D	0.727	prob.delet.	None	None	None	None	N
A/L	0.5402	ambiguous	0.5856	pathogenic	0.443	Stabilizing	0.754	D	0.695	prob.neutral	None	None	None	None	N
A/M	0.598	likely_pathogenic	0.6604	pathogenic	0.305	Stabilizing	0.994	D	0.749	deleterious	None	None	None	None	N
A/N	0.9308	likely_pathogenic	0.9494	pathogenic	-0.77	Destabilizing	0.956	D	0.769	deleterious	None	None	None	None	N
A/P	0.9365	likely_pathogenic	0.9629	pathogenic	0.106	Stabilizing	0.971	D	0.752	deleterious	D	0.624299646	None	None	N
A/Q	0.9462	likely_pathogenic	0.9563	pathogenic	-0.641	Destabilizing	0.978	D	0.753	deleterious	None	None	None	None	N
A/R	0.9661	likely_pathogenic	0.973	pathogenic	-0.818	Destabilizing	0.956	D	0.753	deleterious	None	None	None	None	N
A/S	0.237	likely_benign	0.27	benign	-1.248	Destabilizing	0.698	D	0.637	neutral	N	0.446252385	None	None	N
A/T	0.2581	likely_benign	0.3164	benign	-0.971	Destabilizing	0.032	N	0.484	neutral	D	0.536653701	None	None	N
A/V	0.268	likely_benign	0.308	benign	0.106	Stabilizing	0.126	N	0.489	neutral	N	0.479796228	None	None	N
A/W	0.9847	likely_pathogenic	0.9884	pathogenic	-1.183	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
A/Y	0.9379	likely_pathogenic	0.948	pathogenic	-0.58	Destabilizing	0.993	D	0.767	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.