TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7252	21979;21980;21981	chr2:178723253;178723252;178723251	chr2:179587980;179587979;179587978
N2AB	6935	21028;21029;21030	chr2:178723253;178723252;178723251	chr2:179587980;179587979;179587978
N2A	6008	18247;18248;18249	chr2:178723253;178723252;178723251	chr2:179587980;179587979;179587978
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-57
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1716
• 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/I	rs375714080	-0.195	0.001	D	0.323	0.242	None	gnomAD-4.0.0	1.0949E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43927E-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	0.0887	likely_benign	0.0952	benign	-1.244	Destabilizing	0.001	N	0.144	neutral	D	0.525690855	None	None	N
T/C	0.47	ambiguous	0.4705	ambiguous	-0.826	Destabilizing	0.944	D	0.565	neutral	None	None	None	None	N
T/D	0.4599	ambiguous	0.5078	ambiguous	-0.872	Destabilizing	0.563	D	0.565	neutral	None	None	None	None	N
T/E	0.3342	likely_benign	0.345	ambiguous	-0.75	Destabilizing	0.388	N	0.511	neutral	None	None	None	None	N
T/F	0.2486	likely_benign	0.2941	benign	-0.969	Destabilizing	0.69	D	0.603	neutral	None	None	None	None	N
T/G	0.296	likely_benign	0.3265	benign	-1.597	Destabilizing	0.241	N	0.533	neutral	None	None	None	None	N
T/H	0.296	likely_benign	0.3249	benign	-1.626	Destabilizing	0.944	D	0.597	neutral	None	None	None	None	N
T/I	0.1573	likely_benign	0.1765	benign	-0.344	Destabilizing	0.001	N	0.323	neutral	D	0.528616517	None	None	N
T/K	0.2386	likely_benign	0.2556	benign	-0.63	Destabilizing	0.241	N	0.515	neutral	None	None	None	None	N
T/L	0.1166	likely_benign	0.1313	benign	-0.344	Destabilizing	0.116	N	0.475	neutral	None	None	None	None	N
T/M	0.1088	likely_benign	0.1203	benign	-0.22	Destabilizing	0.69	D	0.579	neutral	None	None	None	None	N
T/N	0.1455	likely_benign	0.1682	benign	-0.956	Destabilizing	0.627	D	0.537	neutral	N	0.489708936	None	None	N
T/P	0.2706	likely_benign	0.2835	benign	-0.613	Destabilizing	0.773	D	0.59	neutral	D	0.52322934	None	None	N
T/Q	0.2561	likely_benign	0.2662	benign	-0.956	Destabilizing	0.69	D	0.594	neutral	None	None	None	None	N
T/R	0.1685	likely_benign	0.1829	benign	-0.579	Destabilizing	0.002	N	0.323	neutral	None	None	None	None	N
T/S	0.1081	likely_benign	0.1207	benign	-1.294	Destabilizing	0.09	N	0.521	neutral	N	0.483228157	None	None	N
T/V	0.134	likely_benign	0.1454	benign	-0.613	Destabilizing	0.116	N	0.492	neutral	None	None	None	None	N
T/W	0.6586	likely_pathogenic	0.6926	pathogenic	-0.932	Destabilizing	0.981	D	0.626	neutral	None	None	None	None	N
T/Y	0.3251	likely_benign	0.3525	ambiguous	-0.651	Destabilizing	0.932	D	0.616	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.