TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33523	100792;100793;100794	chr2:178536180;178536179;178536178	chr2:179400907;179400906;179400905
N2AB	31882	95869;95870;95871	chr2:178536180;178536179;178536178	chr2:179400907;179400906;179400905
N2A	30955	93088;93089;93090	chr2:178536180;178536179;178536178	chr2:179400907;179400906;179400905
N2B	24458	73597;73598;73599	chr2:178536180;178536179;178536178	chr2:179400907;179400906;179400905
Novex-1	24583	73972;73973;73974	chr2:178536180;178536179;178536178	chr2:179400907;179400906;179400905
Novex-2	24650	74173;74174;74175	chr2:178536180;178536179;178536178	chr2:179400907;179400906;179400905
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-158
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.4106
• 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/Q	rs794729558	None	1.0	D	0.793	0.717	0.633466640759	gnomAD-4.0.0	3.18402E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	4.82393E-04	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
P/A	0.9695	likely_pathogenic	0.975	pathogenic	-0.683	Destabilizing	0.996	D	0.746	deleterious	D	0.543022467	None	None	I
P/C	0.9967	likely_pathogenic	0.9972	pathogenic	-0.4	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
P/D	0.9973	likely_pathogenic	0.9974	pathogenic	-0.78	Destabilizing	0.996	D	0.762	deleterious	None	None	None	None	I
P/E	0.9927	likely_pathogenic	0.994	pathogenic	-0.901	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	I
P/F	0.9989	likely_pathogenic	0.999	pathogenic	-0.937	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/G	0.9872	likely_pathogenic	0.988	pathogenic	-0.831	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/H	0.9917	likely_pathogenic	0.9933	pathogenic	-0.517	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/I	0.9912	likely_pathogenic	0.9925	pathogenic	-0.433	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
P/K	0.9941	likely_pathogenic	0.994	pathogenic	-0.653	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
P/L	0.9767	likely_pathogenic	0.9818	pathogenic	-0.433	Destabilizing	1.0	D	0.767	deleterious	D	0.589490625	None	None	I
P/M	0.9953	likely_pathogenic	0.9961	pathogenic	-0.291	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
P/N	0.9953	likely_pathogenic	0.9955	pathogenic	-0.234	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
P/Q	0.9866	likely_pathogenic	0.9886	pathogenic	-0.532	Destabilizing	1.0	D	0.793	deleterious	D	0.547630823	None	None	I
P/R	0.9828	likely_pathogenic	0.9833	pathogenic	-0.066	Destabilizing	1.0	D	0.799	deleterious	D	0.610446164	None	None	I
P/S	0.9879	likely_pathogenic	0.9902	pathogenic	-0.515	Destabilizing	1.0	D	0.767	deleterious	D	0.547123844	None	None	I
P/T	0.9703	likely_pathogenic	0.9761	pathogenic	-0.548	Destabilizing	0.999	D	0.761	deleterious	D	0.610446164	None	None	I
P/V	0.9813	likely_pathogenic	0.9843	pathogenic	-0.482	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
P/W	0.9991	likely_pathogenic	0.9993	pathogenic	-1.038	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
P/Y	0.9983	likely_pathogenic	0.9984	pathogenic	-0.755	Destabilizing	1.0	D	0.828	deleterious	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.