TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8695	26308;26309;26310	chr2:178715103;178715102;178715101	chr2:179579830;179579829;179579828
N2AB	8378	25357;25358;25359	chr2:178715103;178715102;178715101	chr2:179579830;179579829;179579828
N2A	7451	22576;22577;22578	chr2:178715103;178715102;178715101	chr2:179579830;179579829;179579828
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-72
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.4894
• 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/D	rs767736451	0.227	0.126	N	0.223	0.116	0.115124310173	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
N/D	rs767736451	0.227	0.126	N	0.223	0.116	0.115124310173	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
N/D	rs767736451	0.227	0.126	N	0.223	0.116	0.115124310173	gnomAD-4.0.0	9.91551E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39061E-06	1.31752E-04	0
N/K	None	None	0.897	N	0.163	0.15	0.124217242631	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85883E-06	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
N/A	0.3222	likely_benign	0.2862	benign	-0.217	Destabilizing	0.058	N	0.292	neutral	None	None	None	None	N
N/C	0.529	ambiguous	0.4661	ambiguous	-0.042	Destabilizing	0.996	D	0.391	neutral	None	None	None	None	N
N/D	0.1312	likely_benign	0.131	benign	0.217	Stabilizing	0.126	N	0.223	neutral	N	0.452954738	None	None	N
N/E	0.4358	ambiguous	0.4134	ambiguous	0.195	Stabilizing	0.04	N	0.121	neutral	None	None	None	None	N
N/F	0.6603	likely_pathogenic	0.6045	pathogenic	-0.831	Destabilizing	0.996	D	0.372	neutral	None	None	None	None	N
N/G	0.3142	likely_benign	0.284	benign	-0.334	Destabilizing	0.003	N	0.077	neutral	None	None	None	None	N
N/H	0.1612	likely_benign	0.1391	benign	-0.261	Destabilizing	0.986	D	0.358	neutral	N	0.514544701	None	None	N
N/I	0.3447	ambiguous	0.3131	benign	-0.003	Destabilizing	0.959	D	0.398	neutral	N	0.480481867	None	None	N
N/K	0.3399	likely_benign	0.3032	benign	0.154	Stabilizing	0.897	D	0.163	neutral	N	0.513504551	None	None	N
N/L	0.4063	ambiguous	0.3623	ambiguous	-0.003	Destabilizing	0.897	D	0.321	neutral	None	None	None	None	N
N/M	0.4364	ambiguous	0.3996	ambiguous	-0.142	Destabilizing	0.997	D	0.353	neutral	None	None	None	None	N
N/P	0.6993	likely_pathogenic	0.6279	pathogenic	-0.051	Destabilizing	0.868	D	0.361	neutral	None	None	None	None	N
N/Q	0.4006	ambiguous	0.3604	ambiguous	-0.258	Destabilizing	0.938	D	0.297	neutral	None	None	None	None	N
N/R	0.4381	ambiguous	0.381	ambiguous	0.23	Stabilizing	0.92	D	0.301	neutral	None	None	None	None	N
N/S	0.1359	likely_benign	0.1268	benign	-0.15	Destabilizing	0.027	N	0.098	neutral	N	0.508328018	None	None	N
N/T	0.1969	likely_benign	0.1875	benign	-0.037	Destabilizing	0.351	N	0.16	neutral	N	0.511235037	None	None	N
N/V	0.3722	ambiguous	0.3412	ambiguous	-0.051	Destabilizing	0.72	D	0.356	neutral	None	None	None	None	N
N/W	0.8521	likely_pathogenic	0.813	pathogenic	-0.958	Destabilizing	0.999	D	0.467	neutral	None	None	None	None	N
N/Y	0.2038	likely_benign	0.176	benign	-0.607	Destabilizing	0.995	D	0.355	neutral	N	0.469125561	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.