TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7590	22993;22994;22995	chr2:178721895;178721894;178721893	chr2:179586622;179586621;179586620
N2AB	7273	22042;22043;22044	chr2:178721895;178721894;178721893	chr2:179586622;179586621;179586620
N2A	6346	19261;19262;19263	chr2:178721895;178721894;178721893	chr2:179586622;179586621;179586620
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-60
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2651
• 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
T/A	None	None	0.099	D	0.329	0.185	0.28058544554	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/N	rs1486219064	None	0.379	N	0.429	0.301	0.461323234107	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/N	rs1486219064	None	0.379	N	0.429	0.301	0.461323234107	gnomAD-4.0.0	6.57142E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	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
T/A	0.0749	likely_benign	0.0749	benign	-0.758	Destabilizing	0.099	N	0.329	neutral	D	0.536715925	None	None	N
T/C	0.4091	ambiguous	0.4431	ambiguous	-0.572	Destabilizing	0.992	D	0.457	neutral	None	None	None	None	N
T/D	0.4496	ambiguous	0.4322	ambiguous	-1.169	Destabilizing	0.617	D	0.442	neutral	None	None	None	None	N
T/E	0.3411	ambiguous	0.2932	benign	-1.132	Destabilizing	0.617	D	0.401	neutral	None	None	None	None	N
T/F	0.1758	likely_benign	0.1798	benign	-0.68	Destabilizing	0.85	D	0.547	neutral	None	None	None	None	N
T/G	0.2203	likely_benign	0.2308	benign	-1.059	Destabilizing	0.447	N	0.506	neutral	None	None	None	None	N
T/H	0.2411	likely_benign	0.2378	benign	-1.374	Destabilizing	0.977	D	0.537	neutral	None	None	None	None	N
T/I	0.1406	likely_benign	0.1335	benign	-0.033	Destabilizing	0.379	N	0.439	neutral	D	0.537294715	None	None	N
T/K	0.274	likely_benign	0.2225	benign	-0.938	Destabilizing	0.447	N	0.402	neutral	None	None	None	None	N
T/L	0.1082	likely_benign	0.1112	benign	-0.033	Destabilizing	0.25	N	0.468	neutral	None	None	None	None	N
T/M	0.0884	likely_benign	0.0881	benign	0.307	Stabilizing	0.127	N	0.393	neutral	None	None	None	None	N
T/N	0.1299	likely_benign	0.1369	benign	-1.076	Destabilizing	0.379	N	0.429	neutral	N	0.499712569	None	None	N
T/P	0.7462	likely_pathogenic	0.701	pathogenic	-0.242	Destabilizing	0.896	D	0.431	neutral	D	0.541707977	None	None	N
T/Q	0.2202	likely_benign	0.1949	benign	-1.225	Destabilizing	0.85	D	0.433	neutral	None	None	None	None	N
T/R	0.1976	likely_benign	0.1598	benign	-0.7	Destabilizing	0.85	D	0.432	neutral	None	None	None	None	N
T/S	0.0772	likely_benign	0.0847	benign	-1.215	Destabilizing	0.007	N	0.109	neutral	N	0.450001017	None	None	N
T/V	0.1086	likely_benign	0.1055	benign	-0.242	Destabilizing	0.005	N	0.159	neutral	None	None	None	None	N
T/W	0.4938	ambiguous	0.4881	ambiguous	-0.704	Destabilizing	0.992	D	0.569	neutral	None	None	None	None	N
T/Y	0.2531	likely_benign	0.2603	benign	-0.441	Destabilizing	0.92	D	0.558	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.