TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8493	25702;25703;25704	chr2:178717257;178717256;178717255	chr2:179581984;179581983;179581982
N2AB	8176	24751;24752;24753	chr2:178717257;178717256;178717255	chr2:179581984;179581983;179581982
N2A	7249	21970;21971;21972	chr2:178717257;178717256;178717255	chr2:179581984;179581983;179581982
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-70
• Domain position: 38
• Structural Position: 52
• Q(SASA): 1.0098
• 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/I	None	None	0.993	N	0.42	0.355	0.380564188046	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/K	None	None	0.946	N	0.327	0.192	0.181679512989	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85904E-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	0.2479	likely_benign	0.2896	benign	-0.205	Destabilizing	0.2	N	0.327	neutral	None	None	None	None	N
N/C	0.4683	ambiguous	0.5104	ambiguous	0.379	Stabilizing	0.998	D	0.436	neutral	None	None	None	None	N
N/D	0.1523	likely_benign	0.1393	benign	0.125	Stabilizing	0.226	N	0.335	neutral	N	0.488395463	None	None	N
N/E	0.4089	ambiguous	0.4102	ambiguous	0.078	Stabilizing	0.077	N	0.173	neutral	None	None	None	None	N
N/F	0.5645	likely_pathogenic	0.6025	pathogenic	-0.664	Destabilizing	0.994	D	0.409	neutral	None	None	None	None	N
N/G	0.1859	likely_benign	0.2061	benign	-0.35	Destabilizing	0.02	N	0.121	neutral	None	None	None	None	N
N/H	0.1174	likely_benign	0.1244	benign	-0.406	Destabilizing	0.045	N	0.199	neutral	N	0.458440819	None	None	N
N/I	0.3522	ambiguous	0.399	ambiguous	0.082	Stabilizing	0.993	D	0.42	neutral	N	0.504537604	None	None	N
N/K	0.3337	likely_benign	0.3409	ambiguous	0.127	Stabilizing	0.946	D	0.327	neutral	N	0.502538196	None	None	N
N/L	0.297	likely_benign	0.3432	ambiguous	0.082	Stabilizing	0.946	D	0.449	neutral	None	None	None	None	N
N/M	0.3674	ambiguous	0.4251	ambiguous	0.311	Stabilizing	0.999	D	0.399	neutral	None	None	None	None	N
N/P	0.8178	likely_pathogenic	0.8549	pathogenic	0.012	Stabilizing	0.976	D	0.423	neutral	None	None	None	None	N
N/Q	0.29	likely_benign	0.3077	benign	-0.186	Destabilizing	0.968	D	0.349	neutral	None	None	None	None	N
N/R	0.3762	ambiguous	0.3799	ambiguous	0.179	Stabilizing	0.959	D	0.342	neutral	None	None	None	None	N
N/S	0.0746	likely_benign	0.0844	benign	0.032	Stabilizing	0.371	N	0.333	neutral	N	0.507482656	None	None	N
N/T	0.1614	likely_benign	0.1973	benign	0.113	Stabilizing	0.816	D	0.333	neutral	N	0.462035217	None	None	N
N/V	0.3663	ambiguous	0.4173	ambiguous	0.012	Stabilizing	0.839	D	0.43	neutral	None	None	None	None	N
N/W	0.8036	likely_pathogenic	0.8109	pathogenic	-0.719	Destabilizing	0.999	D	0.513	neutral	None	None	None	None	N
N/Y	0.2391	likely_benign	0.2469	benign	-0.428	Destabilizing	0.984	D	0.409	neutral	N	0.492927809	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.