TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15995	48208;48209;48210	chr2:178616906;178616905;178616904	chr2:179481633;179481632;179481631
N2AB	14354	43285;43286;43287	chr2:178616906;178616905;178616904	chr2:179481633;179481632;179481631
N2A	13427	40504;40505;40506	chr2:178616906;178616905;178616904	chr2:179481633;179481632;179481631
N2B	6930	21013;21014;21015	chr2:178616906;178616905;178616904	chr2:179481633;179481632;179481631
Novex-1	7055	21388;21389;21390	chr2:178616906;178616905;178616904	chr2:179481633;179481632;179481631
Novex-2	7122	21589;21590;21591	chr2:178616906;178616905;178616904	chr2:179481633;179481632;179481631
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-109
• Domain position: 28
• Structural Position: 47
• Q(SASA): 0.5517
• 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	rs1205858771	-0.007	0.035	N	0.592	0.186	0.514015564596	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.68161E-04	None	0	None	0	0	0
T/I	rs1205858771	-0.007	0.035	N	0.592	0.186	0.514015564596	gnomAD-4.0.0	4.78025E-06	None	None	None	None	N	None	0	0	None	0	8.34307E-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	0.1068	likely_benign	0.1069	benign	-0.943	Destabilizing	0.042	N	0.449	neutral	D	0.531111131	None	None	N
T/C	0.4643	ambiguous	0.4591	ambiguous	-0.483	Destabilizing	0.883	D	0.582	neutral	None	None	None	None	N
T/D	0.4557	ambiguous	0.443	ambiguous	-0.417	Destabilizing	0.22	N	0.594	neutral	None	None	None	None	N
T/E	0.2711	likely_benign	0.268	benign	-0.355	Destabilizing	0.22	N	0.57	neutral	None	None	None	None	N
T/F	0.2808	likely_benign	0.2683	benign	-0.799	Destabilizing	0.497	N	0.599	neutral	None	None	None	None	N
T/G	0.3674	ambiguous	0.3553	ambiguous	-1.272	Destabilizing	None	N	0.431	neutral	None	None	None	None	N
T/H	0.2178	likely_benign	0.2119	benign	-1.487	Destabilizing	0.859	D	0.588	neutral	None	None	None	None	N
T/I	0.1516	likely_benign	0.1545	benign	-0.135	Destabilizing	0.035	N	0.592	neutral	N	0.513317294	None	None	N
T/K	0.1399	likely_benign	0.1427	benign	-0.771	Destabilizing	0.002	N	0.292	neutral	None	None	None	None	N
T/L	0.1198	likely_benign	0.1251	benign	-0.135	Destabilizing	0.055	N	0.562	neutral	None	None	None	None	N
T/M	0.1291	likely_benign	0.128	benign	0.065	Stabilizing	0.497	N	0.609	neutral	None	None	None	None	N
T/N	0.156	likely_benign	0.1559	benign	-0.858	Destabilizing	0.175	N	0.533	neutral	D	0.615108537	None	None	N
T/P	0.6472	likely_pathogenic	0.6288	pathogenic	-0.371	Destabilizing	0.822	D	0.631	neutral	D	0.616812191	None	None	N
T/Q	0.1933	likely_benign	0.1893	benign	-0.867	Destabilizing	0.497	N	0.63	neutral	None	None	None	None	N
T/R	0.1248	likely_benign	0.1265	benign	-0.675	Destabilizing	0.004	N	0.37	neutral	None	None	None	None	N
T/S	0.1184	likely_benign	0.1148	benign	-1.134	Destabilizing	0.081	N	0.579	neutral	N	0.499095223	None	None	N
T/V	0.1309	likely_benign	0.1359	benign	-0.371	Destabilizing	0.001	N	0.226	neutral	None	None	None	None	N
T/W	0.6562	likely_pathogenic	0.6246	pathogenic	-0.798	Destabilizing	0.958	D	0.609	neutral	None	None	None	None	N
T/Y	0.2939	likely_benign	0.2874	benign	-0.551	Destabilizing	0.667	D	0.601	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.