TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16103	48532;48533;48534	chr2:178616484;178616483;178616482	chr2:179481211;179481210;179481209
N2AB	14462	43609;43610;43611	chr2:178616484;178616483;178616482	chr2:179481211;179481210;179481209
N2A	13535	40828;40829;40830	chr2:178616484;178616483;178616482	chr2:179481211;179481210;179481209
N2B	7038	21337;21338;21339	chr2:178616484;178616483;178616482	chr2:179481211;179481210;179481209
Novex-1	7163	21712;21713;21714	chr2:178616484;178616483;178616482	chr2:179481211;179481210;179481209
Novex-2	7230	21913;21914;21915	chr2:178616484;178616483;178616482	chr2:179481211;179481210;179481209
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: Fn3-4
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4212
• 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	None	None	0.001	N	0.167	0.103	0.258283824007	gnomAD-4.0.0	6.84876E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0021E-07	0	0
T/S	rs1411572700	None	0.003	N	0.158	0.088	0.115124310173	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/S	rs1411572700	None	0.003	N	0.158	0.088	0.115124310173	gnomAD-4.0.0	6.58553E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47271E-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	0.0835	likely_benign	0.0878	benign	-0.703	Destabilizing	None	N	0.095	neutral	N	0.460309703	None	None	N
T/C	0.3779	ambiguous	0.4338	ambiguous	-0.463	Destabilizing	0.94	D	0.307	neutral	None	None	None	None	N
T/D	0.4568	ambiguous	0.4914	ambiguous	0.295	Stabilizing	0.418	N	0.294	neutral	None	None	None	None	N
T/E	0.3202	likely_benign	0.3414	ambiguous	0.293	Stabilizing	0.418	N	0.3	neutral	None	None	None	None	N
T/F	0.2943	likely_benign	0.2972	benign	-0.814	Destabilizing	0.418	N	0.358	neutral	None	None	None	None	N
T/G	0.2229	likely_benign	0.2473	benign	-0.941	Destabilizing	0.129	N	0.281	neutral	None	None	None	None	N
T/H	0.271	likely_benign	0.2966	benign	-1.089	Destabilizing	0.836	D	0.331	neutral	None	None	None	None	N
T/I	0.1732	likely_benign	0.1625	benign	-0.167	Destabilizing	0.001	N	0.167	neutral	N	0.45626025	None	None	N
T/K	0.2598	likely_benign	0.2665	benign	-0.522	Destabilizing	0.264	N	0.305	neutral	None	None	None	None	N
T/L	0.0992	likely_benign	0.1046	benign	-0.167	Destabilizing	0.022	N	0.223	neutral	None	None	None	None	N
T/M	0.0874	likely_benign	0.0912	benign	-0.094	Destabilizing	0.027	N	0.209	neutral	None	None	None	None	N
T/N	0.1124	likely_benign	0.1185	benign	-0.459	Destabilizing	0.213	N	0.204	neutral	N	0.477984237	None	None	N
T/P	0.5101	ambiguous	0.4965	ambiguous	-0.314	Destabilizing	0.523	D	0.34	neutral	D	0.532858515	None	None	N
T/Q	0.2021	likely_benign	0.2153	benign	-0.57	Destabilizing	0.418	N	0.386	neutral	None	None	None	None	N
T/R	0.2198	likely_benign	0.2298	benign	-0.307	Destabilizing	0.418	N	0.336	neutral	None	None	None	None	N
T/S	0.1011	likely_benign	0.1113	benign	-0.786	Destabilizing	0.003	N	0.158	neutral	N	0.452830656	None	None	N
T/V	0.1273	likely_benign	0.1294	benign	-0.314	Destabilizing	0.001	N	0.091	neutral	None	None	None	None	N
T/W	0.6322	likely_pathogenic	0.6571	pathogenic	-0.762	Destabilizing	0.983	D	0.337	neutral	None	None	None	None	N
T/Y	0.3288	likely_benign	0.3535	ambiguous	-0.515	Destabilizing	0.836	D	0.397	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.