TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7084	21475;21476;21477	chr2:178724009;178724008;178724007	chr2:179588736;179588735;179588734
N2AB	6767	20524;20525;20526	chr2:178724009;178724008;178724007	chr2:179588736;179588735;179588734
N2A	5840	17743;17744;17745	chr2:178724009;178724008;178724007	chr2:179588736;179588735;179588734
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-55
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1694
• 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
I/N	rs2078903172	None	0.794	D	0.549	0.639	0.874678355217	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/N	rs2078903172	None	0.794	D	0.549	0.639	0.874678355217	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	2.41196E-05	0	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
I/A	0.6131	likely_pathogenic	0.494	ambiguous	-2.01	Highly Destabilizing	0.129	N	0.383	neutral	None	None	None	None	N
I/C	0.9484	likely_pathogenic	0.9397	pathogenic	-1.101	Destabilizing	0.94	D	0.512	neutral	None	None	None	None	N
I/D	0.9743	likely_pathogenic	0.9694	pathogenic	-2.293	Highly Destabilizing	0.836	D	0.553	neutral	None	None	None	None	N
I/E	0.9359	likely_pathogenic	0.9226	pathogenic	-2.038	Highly Destabilizing	0.836	D	0.559	neutral	None	None	None	None	N
I/F	0.4144	ambiguous	0.3781	ambiguous	-1.21	Destabilizing	0.351	N	0.509	neutral	D	0.554634445	None	None	N
I/G	0.9275	likely_pathogenic	0.9044	pathogenic	-2.548	Highly Destabilizing	0.593	D	0.529	neutral	None	None	None	None	N
I/H	0.9368	likely_pathogenic	0.9273	pathogenic	-2.08	Highly Destabilizing	0.983	D	0.549	neutral	None	None	None	None	N
I/K	0.8953	likely_pathogenic	0.8893	pathogenic	-1.354	Destabilizing	0.593	D	0.53	neutral	None	None	None	None	N
I/L	0.1394	likely_benign	0.117	benign	-0.45	Destabilizing	None	N	0.095	neutral	N	0.490148555	None	None	N
I/M	0.1518	likely_benign	0.1296	benign	-0.385	Destabilizing	0.047	N	0.287	neutral	D	0.526401652	None	None	N
I/N	0.8159	likely_pathogenic	0.804	pathogenic	-1.786	Destabilizing	0.794	D	0.549	neutral	D	0.537544148	None	None	N
I/P	0.9226	likely_pathogenic	0.8903	pathogenic	-0.952	Destabilizing	0.94	D	0.549	neutral	None	None	None	None	N
I/Q	0.902	likely_pathogenic	0.8894	pathogenic	-1.577	Destabilizing	0.836	D	0.559	neutral	None	None	None	None	N
I/R	0.8263	likely_pathogenic	0.8128	pathogenic	-1.312	Destabilizing	0.836	D	0.549	neutral	None	None	None	None	N
I/S	0.7988	likely_pathogenic	0.7482	pathogenic	-2.434	Highly Destabilizing	0.213	N	0.479	neutral	D	0.530453804	None	None	N
I/T	0.5543	ambiguous	0.4296	ambiguous	-2.023	Highly Destabilizing	0.007	N	0.259	neutral	D	0.527665419	None	None	N
I/V	0.1435	likely_benign	0.1208	benign	-0.952	Destabilizing	0.001	N	0.123	neutral	N	0.505776942	None	None	N
I/W	0.9365	likely_pathogenic	0.9342	pathogenic	-1.6	Destabilizing	0.983	D	0.575	neutral	None	None	None	None	N
I/Y	0.8284	likely_pathogenic	0.8197	pathogenic	-1.218	Destabilizing	0.836	D	0.523	neutral	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.