TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7150	21673;21674;21675	chr2:178723652;178723651;178723650	chr2:179588379;179588378;179588377
N2AB	6833	20722;20723;20724	chr2:178723652;178723651;178723650	chr2:179588379;179588378;179588377
N2A	5906	17941;17942;17943	chr2:178723652;178723651;178723650	chr2:179588379;179588378;179588377
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-56
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4949
• Predicted PPI site: I

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
P/S	rs1248770778	None	0.896	N	0.404	0.265	0.184867976434	gnomAD-4.0.0	3.21365E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88063E-06	0	3.04971E-05

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
P/A	0.115	likely_benign	0.1145	benign	-1.093	Destabilizing	0.896	D	0.407	neutral	N	0.477581037	None	None	I
P/C	0.6276	likely_pathogenic	0.6561	pathogenic	-0.878	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
P/D	0.705	likely_pathogenic	0.726	pathogenic	-0.805	Destabilizing	0.988	D	0.411	neutral	None	None	None	None	I
P/E	0.3818	ambiguous	0.3858	ambiguous	-0.825	Destabilizing	0.976	D	0.386	neutral	None	None	None	None	I
P/F	0.6473	likely_pathogenic	0.6832	pathogenic	-0.805	Destabilizing	0.976	D	0.621	neutral	None	None	None	None	I
P/G	0.4832	ambiguous	0.5006	ambiguous	-1.369	Destabilizing	0.988	D	0.471	neutral	None	None	None	None	I
P/H	0.309	likely_benign	0.3373	benign	-0.791	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	I
P/I	0.3691	ambiguous	0.3697	ambiguous	-0.457	Destabilizing	0.952	D	0.55	neutral	None	None	None	None	I
P/K	0.3939	ambiguous	0.4174	ambiguous	-1.047	Destabilizing	0.261	N	0.291	neutral	None	None	None	None	I
P/L	0.1417	likely_benign	0.1571	benign	-0.457	Destabilizing	0.026	N	0.371	neutral	N	0.493531924	None	None	I
P/M	0.4177	ambiguous	0.4385	ambiguous	-0.474	Destabilizing	0.976	D	0.552	neutral	None	None	None	None	I
P/N	0.5589	ambiguous	0.5768	pathogenic	-0.86	Destabilizing	0.988	D	0.545	neutral	None	None	None	None	I
P/Q	0.2305	likely_benign	0.2427	benign	-1.014	Destabilizing	0.968	D	0.389	neutral	N	0.500132609	None	None	I
P/R	0.2296	likely_benign	0.2438	benign	-0.511	Destabilizing	0.938	D	0.533	neutral	N	0.502556839	None	None	I
P/S	0.2095	likely_benign	0.2165	benign	-1.344	Destabilizing	0.896	D	0.404	neutral	N	0.479122619	None	None	I
P/T	0.1448	likely_benign	0.1451	benign	-1.251	Destabilizing	0.984	D	0.399	neutral	N	0.456861835	None	None	I
P/V	0.2603	likely_benign	0.2569	benign	-0.633	Destabilizing	0.851	D	0.481	neutral	None	None	None	None	I
P/W	0.727	likely_pathogenic	0.7646	pathogenic	-0.956	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
P/Y	0.5895	likely_pathogenic	0.6346	pathogenic	-0.674	Destabilizing	0.988	D	0.625	neutral	None	None	None	None	I

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.