TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5546	16861;16862;16863	chr2:178732333;178732332;178732331	chr2:179597060;179597059;179597058
N2AB	5229	15910;15911;15912	chr2:178732333;178732332;178732331	chr2:179597060;179597059;179597058
N2A	4302	13129;13130;13131	chr2:178732333;178732332;178732331	chr2:179597060;179597059;179597058
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-39
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4163
• 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
V/G	rs903298127	None	0.117	N	0.285	0.215	0.654939258183	gnomAD-4.0.0	1.62235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91455E-06	0	0
V/I	rs2154310117	None	None	N	0.135	0.06	0.110078149338	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	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
V/A	0.0877	likely_benign	0.0955	benign	-1.003	Destabilizing	0.027	N	0.217	neutral	N	0.451324021	None	None	N
V/C	0.5381	ambiguous	0.6288	pathogenic	-0.747	Destabilizing	0.935	D	0.295	neutral	None	None	None	None	N
V/D	0.2114	likely_benign	0.2267	benign	-0.665	Destabilizing	0.317	N	0.322	neutral	N	0.452844958	None	None	N
V/E	0.1545	likely_benign	0.1606	benign	-0.738	Destabilizing	0.081	N	0.3	neutral	None	None	None	None	N
V/F	0.1176	likely_benign	0.1394	benign	-0.928	Destabilizing	0.317	N	0.335	neutral	N	0.492305471	None	None	N
V/G	0.1525	likely_benign	0.1645	benign	-1.219	Destabilizing	0.117	N	0.285	neutral	N	0.482052029	None	None	N
V/H	0.2796	likely_benign	0.3274	benign	-0.67	Destabilizing	0.935	D	0.309	neutral	None	None	None	None	N
V/I	0.0624	likely_benign	0.0696	benign	-0.552	Destabilizing	None	N	0.135	neutral	N	0.421479825	None	None	N
V/K	0.1554	likely_benign	0.1672	benign	-0.863	Destabilizing	0.001	N	0.243	neutral	None	None	None	None	N
V/L	0.0963	likely_benign	0.1131	benign	-0.552	Destabilizing	0.004	N	0.142	neutral	N	0.489627614	None	None	N
V/M	0.0906	likely_benign	0.1057	benign	-0.45	Destabilizing	0.016	N	0.147	neutral	None	None	None	None	N
V/N	0.1588	likely_benign	0.1906	benign	-0.59	Destabilizing	0.38	N	0.319	neutral	None	None	None	None	N
V/P	0.3957	ambiguous	0.4743	ambiguous	-0.666	Destabilizing	0.555	D	0.315	neutral	None	None	None	None	N
V/Q	0.1545	likely_benign	0.1624	benign	-0.829	Destabilizing	0.38	N	0.33	neutral	None	None	None	None	N
V/R	0.1183	likely_benign	0.1311	benign	-0.268	Destabilizing	0.235	N	0.329	neutral	None	None	None	None	N
V/S	0.1063	likely_benign	0.1173	benign	-1.036	Destabilizing	0.081	N	0.273	neutral	None	None	None	None	N
V/T	0.0772	likely_benign	0.0865	benign	-1.006	Destabilizing	None	N	0.095	neutral	None	None	None	None	N
V/W	0.5132	ambiguous	0.6006	pathogenic	-1.018	Destabilizing	0.935	D	0.345	neutral	None	None	None	None	N
V/Y	0.3331	likely_benign	0.4091	ambiguous	-0.749	Destabilizing	0.555	D	0.317	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.