TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8463	25612;25613;25614	chr2:178717347;178717346;178717345	chr2:179582074;179582073;179582072
N2AB	8146	24661;24662;24663	chr2:178717347;178717346;178717345	chr2:179582074;179582073;179582072
N2A	7219	21880;21881;21882	chr2:178717347;178717346;178717345	chr2:179582074;179582073;179582072
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-70
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5875
• 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/I	rs767424522	0.112	0.018	N	0.419	0.161	0.279776271856	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/I	rs767424522	0.112	0.018	N	0.419	0.161	0.279776271856	gnomAD-4.0.0	1.59345E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43406E-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	0.0992	likely_benign	0.1027	benign	-0.559	Destabilizing	0.003	N	0.125	neutral	N	0.440570671	None	None	N
V/C	0.7017	likely_pathogenic	0.6981	pathogenic	-0.704	Destabilizing	0.984	D	0.529	neutral	None	None	None	None	N
V/D	0.169	likely_benign	0.1587	benign	-0.127	Destabilizing	0.479	N	0.535	neutral	None	None	None	None	N
V/E	0.1351	likely_benign	0.1187	benign	-0.206	Destabilizing	None	N	0.294	neutral	N	0.409266329	None	None	N
V/F	0.1226	likely_benign	0.1302	benign	-0.598	Destabilizing	0.829	D	0.565	neutral	None	None	None	None	N
V/G	0.1207	likely_benign	0.1231	benign	-0.731	Destabilizing	0.652	D	0.535	neutral	N	0.497560104	None	None	N
V/H	0.3435	ambiguous	0.35	ambiguous	-0.243	Destabilizing	0.875	D	0.563	neutral	None	None	None	None	N
V/I	0.073	likely_benign	0.077	benign	-0.242	Destabilizing	0.018	N	0.419	neutral	N	0.499349615	None	None	N
V/K	0.1867	likely_benign	0.1712	benign	-0.495	Destabilizing	0.245	N	0.526	neutral	None	None	None	None	N
V/L	0.1103	likely_benign	0.1194	benign	-0.242	Destabilizing	None	N	0.135	neutral	N	0.471605654	None	None	N
V/M	0.1	likely_benign	0.1095	benign	-0.421	Destabilizing	0.776	D	0.491	neutral	None	None	None	None	N
V/N	0.1349	likely_benign	0.1491	benign	-0.302	Destabilizing	0.252	N	0.57	neutral	None	None	None	None	N
V/P	0.3896	ambiguous	0.3629	ambiguous	-0.312	Destabilizing	0.406	N	0.564	neutral	None	None	None	None	N
V/Q	0.166	likely_benign	0.1613	benign	-0.478	Destabilizing	0.447	N	0.572	neutral	None	None	None	None	N
V/R	0.18	likely_benign	0.177	benign	-0.04	Destabilizing	0.829	D	0.569	neutral	None	None	None	None	N
V/S	0.1065	likely_benign	0.1176	benign	-0.717	Destabilizing	0.272	N	0.509	neutral	None	None	None	None	N
V/T	0.1112	likely_benign	0.1168	benign	-0.687	Destabilizing	0.231	N	0.381	neutral	None	None	None	None	N
V/W	0.6966	likely_pathogenic	0.6938	pathogenic	-0.701	Destabilizing	0.997	D	0.584	neutral	None	None	None	None	N
V/Y	0.4008	ambiguous	0.4097	ambiguous	-0.4	Destabilizing	0.908	D	0.569	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.