TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6519	19780;19781;19782	chr2:178728269;178728268;178728267	chr2:179592996;179592995;179592994
N2AB	6202	18829;18830;18831	chr2:178728269;178728268;178728267	chr2:179592996;179592995;179592994
N2A	5275	16048;16049;16050	chr2:178728269;178728268;178728267	chr2:179592996;179592995;179592994
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-49
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.7435
• 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
K/I	None	None	0.772	N	0.343	0.423	0.650812743361	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
K/A	0.2883	likely_benign	0.3332	benign	-0.067	Destabilizing	0.209	N	0.369	neutral	None	None	None	None	N
K/C	0.6117	likely_pathogenic	0.6596	pathogenic	-0.39	Destabilizing	0.991	D	0.309	neutral	None	None	None	None	N
K/D	0.3885	ambiguous	0.4624	ambiguous	0.116	Stabilizing	0.39	N	0.376	neutral	None	None	None	None	N
K/E	0.1003	likely_benign	0.1173	benign	0.158	Stabilizing	0.166	N	0.373	neutral	N	0.517492659	None	None	N
K/F	0.6296	likely_pathogenic	0.6599	pathogenic	-0.124	Destabilizing	0.965	D	0.337	neutral	None	None	None	None	N
K/G	0.4202	ambiguous	0.4709	ambiguous	-0.307	Destabilizing	0.209	N	0.367	neutral	None	None	None	None	N
K/H	0.2591	likely_benign	0.2845	benign	-0.492	Destabilizing	0.901	D	0.357	neutral	None	None	None	None	N
K/I	0.2001	likely_benign	0.222	benign	0.497	Stabilizing	0.772	D	0.343	neutral	N	0.494672913	None	None	N
K/L	0.2599	likely_benign	0.2943	benign	0.497	Stabilizing	0.561	D	0.379	neutral	None	None	None	None	N
K/M	0.1527	likely_benign	0.175	benign	0.101	Stabilizing	0.965	D	0.36	neutral	None	None	None	None	N
K/N	0.2175	likely_benign	0.2622	benign	-0.035	Destabilizing	0.003	N	0.267	neutral	N	0.474686031	None	None	N
K/P	0.9156	likely_pathogenic	0.9259	pathogenic	0.338	Stabilizing	0.722	D	0.399	neutral	None	None	None	None	N
K/Q	0.1011	likely_benign	0.1134	benign	-0.119	Destabilizing	0.036	N	0.239	neutral	N	0.480417138	None	None	N
K/R	0.0837	likely_benign	0.0815	benign	-0.152	Destabilizing	0.003	N	0.301	neutral	D	0.523093267	None	None	N
K/S	0.2922	likely_benign	0.3558	ambiguous	-0.527	Destabilizing	0.047	N	0.245	neutral	None	None	None	None	N
K/T	0.1298	likely_benign	0.1561	benign	-0.319	Destabilizing	0.005	N	0.195	neutral	N	0.51734073	None	None	N
K/V	0.1887	likely_benign	0.2169	benign	0.338	Stabilizing	0.561	D	0.402	neutral	None	None	None	None	N
K/W	0.686	likely_pathogenic	0.7152	pathogenic	-0.142	Destabilizing	0.991	D	0.331	neutral	None	None	None	None	N
K/Y	0.5139	ambiguous	0.5442	ambiguous	0.194	Stabilizing	0.965	D	0.348	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.