TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17705	53338;53339;53340	chr2:178607575;178607574;178607573	chr2:179472302;179472301;179472300
N2AB	16064	48415;48416;48417	chr2:178607575;178607574;178607573	chr2:179472302;179472301;179472300
N2A	15137	45634;45635;45636	chr2:178607575;178607574;178607573	chr2:179472302;179472301;179472300
N2B	8640	26143;26144;26145	chr2:178607575;178607574;178607573	chr2:179472302;179472301;179472300
Novex-1	8765	26518;26519;26520	chr2:178607575;178607574;178607573	chr2:179472302;179472301;179472300
Novex-2	8832	26719;26720;26721	chr2:178607575;178607574;178607573	chr2:179472302;179472301;179472300
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-113
• Domain position: 29
• Structural Position: 47
• Q(SASA): 0.3056
• 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	None	None	0.101	N	0.41	0.067	0.318252033908	gnomAD-4.0.0	4.77693E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72138E-06	1.43303E-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	0.1617	likely_benign	0.1399	benign	-0.812	Destabilizing	0.001	N	0.161	neutral	N	0.505755513	None	None	N
V/C	0.6604	likely_pathogenic	0.6531	pathogenic	-0.767	Destabilizing	0.94	D	0.511	neutral	None	None	None	None	N
V/D	0.2252	likely_benign	0.2125	benign	-0.351	Destabilizing	0.129	N	0.481	neutral	None	None	None	None	N
V/E	0.1495	likely_benign	0.1402	benign	-0.404	Destabilizing	0.001	N	0.289	neutral	N	0.476181967	None	None	N
V/F	0.1606	likely_benign	0.1597	benign	-0.717	Destabilizing	0.557	D	0.575	neutral	None	None	None	None	N
V/G	0.2121	likely_benign	0.197	benign	-1.033	Destabilizing	0.101	N	0.464	neutral	N	0.48570601	None	None	N
V/H	0.3864	ambiguous	0.3818	ambiguous	-0.434	Destabilizing	0.836	D	0.569	neutral	None	None	None	None	N
V/I	0.0793	likely_benign	0.079	benign	-0.348	Destabilizing	0.101	N	0.41	neutral	N	0.483977518	None	None	N
V/K	0.2097	likely_benign	0.2	benign	-0.638	Destabilizing	0.004	N	0.289	neutral	None	None	None	None	N
V/L	0.1809	likely_benign	0.1706	benign	-0.348	Destabilizing	0.001	N	0.214	neutral	N	0.493770437	None	None	N
V/M	0.1341	likely_benign	0.1263	benign	-0.437	Destabilizing	0.716	D	0.463	neutral	None	None	None	None	N
V/N	0.1699	likely_benign	0.1632	benign	-0.471	Destabilizing	0.418	N	0.535	neutral	None	None	None	None	N
V/P	0.9163	likely_pathogenic	0.8963	pathogenic	-0.466	Destabilizing	0.593	D	0.555	neutral	None	None	None	None	N
V/Q	0.1983	likely_benign	0.1869	benign	-0.646	Destabilizing	0.264	N	0.555	neutral	None	None	None	None	N
V/R	0.225	likely_benign	0.2206	benign	-0.128	Destabilizing	0.264	N	0.562	neutral	None	None	None	None	N
V/S	0.1543	likely_benign	0.1404	benign	-0.941	Destabilizing	0.012	N	0.295	neutral	None	None	None	None	N
V/T	0.1272	likely_benign	0.1146	benign	-0.878	Destabilizing	0.001	N	0.156	neutral	None	None	None	None	N
V/W	0.7551	likely_pathogenic	0.7526	pathogenic	-0.819	Destabilizing	0.983	D	0.587	neutral	None	None	None	None	N
V/Y	0.423	ambiguous	0.4255	ambiguous	-0.521	Destabilizing	0.836	D	0.551	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.