TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8331	25216;25217;25218	chr2:178718015;178718014;178718013	chr2:179582742;179582741;179582740
N2AB	8014	24265;24266;24267	chr2:178718015;178718014;178718013	chr2:179582742;179582741;179582740
N2A	7087	21484;21485;21486	chr2:178718015;178718014;178718013	chr2:179582742;179582741;179582740
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-68
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2797
• Predicted PPI site: I

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/E	rs773888026	-1.278	0.064	N	0.544	0.235	0.55973633643	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
V/E	rs773888026	-1.278	0.064	N	0.544	0.235	0.55973633643	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	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	0.0933	likely_benign	0.0938	benign	-1.021	Destabilizing	0.034	N	0.411	neutral	N	0.382791803	None	None	I
V/C	0.654	likely_pathogenic	0.7423	pathogenic	-0.79	Destabilizing	0.949	D	0.527	neutral	None	None	None	None	I
V/D	0.2446	likely_benign	0.2499	benign	-0.451	Destabilizing	0.663	D	0.607	neutral	None	None	None	None	I
V/E	0.1836	likely_benign	0.1846	benign	-0.505	Destabilizing	0.064	N	0.544	neutral	N	0.411189126	None	None	I
V/F	0.1388	likely_benign	0.1563	benign	-0.92	Destabilizing	0.598	D	0.558	neutral	None	None	None	None	I
V/G	0.1626	likely_benign	0.1784	benign	-1.27	Destabilizing	0.223	N	0.581	neutral	N	0.408306323	None	None	I
V/H	0.4437	ambiguous	0.4914	ambiguous	-0.753	Destabilizing	0.961	D	0.603	neutral	None	None	None	None	I
V/I	0.0689	likely_benign	0.072	benign	-0.474	Destabilizing	None	N	0.135	neutral	None	None	None	None	I
V/K	0.2406	likely_benign	0.2634	benign	-0.782	Destabilizing	0.166	N	0.545	neutral	None	None	None	None	I
V/L	0.1609	likely_benign	0.1821	benign	-0.474	Destabilizing	0.002	N	0.386	neutral	N	0.470970935	None	None	I
V/M	0.1052	likely_benign	0.1202	benign	-0.358	Destabilizing	0.445	N	0.509	neutral	N	0.458174996	None	None	I
V/N	0.1996	likely_benign	0.2114	benign	-0.509	Destabilizing	0.094	N	0.609	neutral	None	None	None	None	I
V/P	0.7116	likely_pathogenic	0.779	pathogenic	-0.62	Destabilizing	0.173	N	0.581	neutral	None	None	None	None	I
V/Q	0.2406	likely_benign	0.2562	benign	-0.709	Destabilizing	0.5	D	0.594	neutral	None	None	None	None	I
V/R	0.1995	likely_benign	0.2191	benign	-0.264	Destabilizing	0.598	D	0.625	neutral	None	None	None	None	I
V/S	0.1181	likely_benign	0.1204	benign	-1.047	Destabilizing	0.001	N	0.315	neutral	None	None	None	None	I
V/T	0.1049	likely_benign	0.1017	benign	-0.986	Destabilizing	0.001	N	0.202	neutral	None	None	None	None	I
V/W	0.6779	likely_pathogenic	0.7383	pathogenic	-1.023	Destabilizing	0.989	D	0.658	neutral	None	None	None	None	I
V/Y	0.4277	ambiguous	0.4742	ambiguous	-0.731	Destabilizing	0.751	D	0.553	neutral	None	None	None	None	I

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.