TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24723	74392;74393;74394	chr2:178571965;178571964;178571963	chr2:179436692;179436691;179436690
N2AB	23082	69469;69470;69471	chr2:178571965;178571964;178571963	chr2:179436692;179436691;179436690
N2A	22155	66688;66689;66690	chr2:178571965;178571964;178571963	chr2:179436692;179436691;179436690
N2B	15658	47197;47198;47199	chr2:178571965;178571964;178571963	chr2:179436692;179436691;179436690
Novex-1	15783	47572;47573;47574	chr2:178571965;178571964;178571963	chr2:179436692;179436691;179436690
Novex-2	15850	47773;47774;47775	chr2:178571965;178571964;178571963	chr2:179436692;179436691;179436690
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-133
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.305
• 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
N/S	rs1708346317	None	None	N	0.074	0.117	0.112648838833	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	6.07533E-05	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
N/A	0.2585	likely_benign	0.2491	benign	-0.717	Destabilizing	0.007	N	0.311	neutral	None	None	None	None	N
N/C	0.3365	likely_benign	0.3393	benign	0.068	Stabilizing	0.356	N	0.442	neutral	None	None	None	None	N
N/D	0.141	likely_benign	0.1489	benign	0.188	Stabilizing	0.024	N	0.281	neutral	N	0.464082248	None	None	N
N/E	0.4035	ambiguous	0.4274	ambiguous	0.254	Stabilizing	0.031	N	0.256	neutral	None	None	None	None	N
N/F	0.7147	likely_pathogenic	0.7186	pathogenic	-0.73	Destabilizing	0.356	N	0.485	neutral	None	None	None	None	N
N/G	0.2275	likely_benign	0.2175	benign	-1.002	Destabilizing	0.016	N	0.287	neutral	None	None	None	None	N
N/H	0.1053	likely_benign	0.1042	benign	-0.742	Destabilizing	0.56	D	0.401	neutral	D	0.527536294	None	None	N
N/I	0.5087	ambiguous	0.5225	ambiguous	-0.017	Destabilizing	0.029	N	0.463	neutral	N	0.496986636	None	None	N
N/K	0.2807	likely_benign	0.2833	benign	0.073	Stabilizing	0.024	N	0.259	neutral	N	0.496786526	None	None	N
N/L	0.3778	ambiguous	0.3776	ambiguous	-0.017	Destabilizing	0.016	N	0.393	neutral	None	None	None	None	N
N/M	0.4624	ambiguous	0.4731	ambiguous	0.211	Stabilizing	0.356	N	0.445	neutral	None	None	None	None	N
N/P	0.354	ambiguous	0.364	ambiguous	-0.221	Destabilizing	0.136	N	0.457	neutral	None	None	None	None	N
N/Q	0.3296	likely_benign	0.3295	benign	-0.441	Destabilizing	0.072	N	0.319	neutral	None	None	None	None	N
N/R	0.3129	likely_benign	0.3134	benign	0.031	Stabilizing	0.072	N	0.238	neutral	None	None	None	None	N
N/S	0.0738	likely_benign	0.0707	benign	-0.526	Destabilizing	None	N	0.074	neutral	N	0.440242597	None	None	N
N/T	0.1162	likely_benign	0.1099	benign	-0.261	Destabilizing	None	N	0.093	neutral	N	0.496135952	None	None	N
N/V	0.456	ambiguous	0.4609	ambiguous	-0.221	Destabilizing	0.016	N	0.427	neutral	None	None	None	None	N
N/W	0.8328	likely_pathogenic	0.8227	pathogenic	-0.546	Destabilizing	0.864	D	0.467	neutral	None	None	None	None	N
N/Y	0.2652	likely_benign	0.2561	benign	-0.308	Destabilizing	0.295	N	0.463	neutral	N	0.503988076	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.