TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7703	23332;23333;23334	chr2:178720655;178720654;178720653	chr2:179585382;179585381;179585380
N2AB	7386	22381;22382;22383	chr2:178720655;178720654;178720653	chr2:179585382;179585381;179585380
N2A	6459	19600;19601;19602	chr2:178720655;178720654;178720653	chr2:179585382;179585381;179585380
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-62
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4348
• 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	rs1318077959	-0.088	None	N	0.199	0.106	0.180583059064	gnomAD-2.1.1	4.56E-06	None	None	None	None	N	None	0	0	None	0	6.18E-05	None	0	None	0	0	0
V/I	rs1318077959	-0.088	None	N	0.199	0.106	0.180583059064	gnomAD-4.0.0	3.34496E-06	None	None	None	None	N	None	0	0	None	0	5.59441E-05	None	0	0	0	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
V/A	0.1473	likely_benign	0.1194	benign	-0.824	Destabilizing	0.063	N	0.32	neutral	N	0.500581766	None	None	N
V/C	0.6699	likely_pathogenic	0.6157	pathogenic	-0.819	Destabilizing	0.972	D	0.462	neutral	None	None	None	None	N
V/D	0.3168	likely_benign	0.2776	benign	-0.016	Destabilizing	0.286	N	0.527	neutral	N	0.518610167	None	None	N
V/E	0.2307	likely_benign	0.2051	benign	-0.045	Destabilizing	0.005	N	0.297	neutral	None	None	None	None	N
V/F	0.1372	likely_benign	0.119	benign	-0.616	Destabilizing	0.679	D	0.519	neutral	N	0.487961973	None	None	N
V/G	0.2082	likely_benign	0.1815	benign	-1.08	Destabilizing	0.52	D	0.509	neutral	N	0.497622201	None	None	N
V/H	0.387	ambiguous	0.3404	ambiguous	-0.499	Destabilizing	0.979	D	0.546	neutral	None	None	None	None	N
V/I	0.0689	likely_benign	0.0659	benign	-0.259	Destabilizing	None	N	0.199	neutral	N	0.489039408	None	None	N
V/K	0.2428	likely_benign	0.2242	benign	-0.576	Destabilizing	0.272	N	0.488	neutral	None	None	None	None	N
V/L	0.1302	likely_benign	0.1062	benign	-0.259	Destabilizing	None	N	0.169	neutral	D	0.523709342	None	None	N
V/M	0.1189	likely_benign	0.1011	benign	-0.382	Destabilizing	0.667	D	0.457	neutral	None	None	None	None	N
V/N	0.1801	likely_benign	0.1495	benign	-0.418	Destabilizing	0.163	N	0.548	neutral	None	None	None	None	N
V/P	0.8921	likely_pathogenic	0.8587	pathogenic	-0.41	Destabilizing	0.283	N	0.56	neutral	None	None	None	None	N
V/Q	0.2208	likely_benign	0.1945	benign	-0.539	Destabilizing	0.482	N	0.552	neutral	None	None	None	None	N
V/R	0.1986	likely_benign	0.1854	benign	-0.163	Destabilizing	0.737	D	0.566	neutral	None	None	None	None	N
V/S	0.1381	likely_benign	0.1182	benign	-0.991	Destabilizing	0.017	N	0.306	neutral	None	None	None	None	N
V/T	0.135	likely_benign	0.1098	benign	-0.895	Destabilizing	0.001	N	0.138	neutral	None	None	None	None	N
V/W	0.7681	likely_pathogenic	0.7153	pathogenic	-0.728	Destabilizing	0.994	D	0.637	neutral	None	None	None	None	N
V/Y	0.4218	ambiguous	0.3685	ambiguous	-0.418	Destabilizing	0.85	D	0.507	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.