TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17662	53209;53210;53211	chr2:178607803;178607802;178607801	chr2:179472530;179472529;179472528
N2AB	16021	48286;48287;48288	chr2:178607803;178607802;178607801	chr2:179472530;179472529;179472528
N2A	15094	45505;45506;45507	chr2:178607803;178607802;178607801	chr2:179472530;179472529;179472528
N2B	8597	26014;26015;26016	chr2:178607803;178607802;178607801	chr2:179472530;179472529;179472528
Novex-1	8722	26389;26390;26391	chr2:178607803;178607802;178607801	chr2:179472530;179472529;179472528
Novex-2	8789	26590;26591;26592	chr2:178607803;178607802;178607801	chr2:179472530;179472529;179472528
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-16
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.3133
• 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	0.688	N	0.36	0.157	0.238705975628	gnomAD-4.0.0	1.59297E-06	None	None	None	None	N	None	0	0	None	0	2.78443E-05	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
T/A	0.1022	likely_benign	0.0934	benign	-0.463	Destabilizing	0.688	D	0.36	neutral	N	0.436374706	None	None	N
T/C	0.4572	ambiguous	0.4408	ambiguous	-0.263	Destabilizing	0.998	D	0.361	neutral	None	None	None	None	N
T/D	0.6499	likely_pathogenic	0.5907	pathogenic	0.034	Stabilizing	0.994	D	0.421	neutral	None	None	None	None	N
T/E	0.3865	ambiguous	0.3428	ambiguous	-0.029	Destabilizing	0.994	D	0.405	neutral	None	None	None	None	N
T/F	0.3408	ambiguous	0.2969	benign	-0.855	Destabilizing	0.009	N	0.355	neutral	None	None	None	None	N
T/G	0.4654	ambiguous	0.4168	ambiguous	-0.628	Destabilizing	0.978	D	0.48	neutral	None	None	None	None	N
T/H	0.2973	likely_benign	0.2818	benign	-0.941	Destabilizing	0.998	D	0.458	neutral	None	None	None	None	N
T/I	0.1728	likely_benign	0.1619	benign	-0.14	Destabilizing	0.067	N	0.295	neutral	N	0.398240393	None	None	N
T/K	0.1564	likely_benign	0.1516	benign	-0.424	Destabilizing	0.994	D	0.419	neutral	None	None	None	None	N
T/L	0.13	likely_benign	0.1202	benign	-0.14	Destabilizing	0.594	D	0.471	neutral	None	None	None	None	N
T/M	0.103	likely_benign	0.0956	benign	0.129	Stabilizing	0.981	D	0.379	neutral	None	None	None	None	N
T/N	0.2074	likely_benign	0.1905	benign	-0.225	Destabilizing	0.991	D	0.401	neutral	N	0.4556539	None	None	N
T/P	0.1916	likely_benign	0.1616	benign	-0.218	Destabilizing	0.991	D	0.44	neutral	N	0.455827259	None	None	N
T/Q	0.2312	likely_benign	0.2053	benign	-0.481	Destabilizing	0.994	D	0.363	neutral	None	None	None	None	N
T/R	0.1414	likely_benign	0.1345	benign	-0.123	Destabilizing	0.994	D	0.439	neutral	None	None	None	None	N
T/S	0.1865	likely_benign	0.1649	benign	-0.457	Destabilizing	0.971	D	0.401	neutral	N	0.454787109	None	None	N
T/V	0.1453	likely_benign	0.1359	benign	-0.218	Destabilizing	0.594	D	0.413	neutral	None	None	None	None	N
T/W	0.6973	likely_pathogenic	0.6495	pathogenic	-0.819	Destabilizing	0.998	D	0.483	neutral	None	None	None	None	N
T/Y	0.4142	ambiguous	0.3754	ambiguous	-0.552	Destabilizing	0.925	D	0.503	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.