TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13793	41602;41603;41604	chr2:178636194;178636193;178636192	chr2:179500921;179500920;179500919
N2AB	12152	36679;36680;36681	chr2:178636194;178636193;178636192	chr2:179500921;179500920;179500919
N2A	11225	33898;33899;33900	chr2:178636194;178636193;178636192	chr2:179500921;179500920;179500919
N2B	4728	14407;14408;14409	chr2:178636194;178636193;178636192	chr2:179500921;179500920;179500919
Novex-1	4853	14782;14783;14784	chr2:178636194;178636193;178636192	chr2:179500921;179500920;179500919
Novex-2	4920	14983;14984;14985	chr2:178636194;178636193;178636192	chr2:179500921;179500920;179500919
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-88
• Domain position: 14
• Structural Position: 18
• Q(SASA): 0.608
• 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/A	None	None	0.425	N	0.299	0.231	0.319686207203	gnomAD-4.0.0	1.37447E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80516E-06	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	0.6307	likely_pathogenic	0.6941	pathogenic	-0.828	Destabilizing	0.425	N	0.299	neutral	N	0.349016953	None	None	N
V/C	0.933	likely_pathogenic	0.9437	pathogenic	-0.764	Destabilizing	0.995	D	0.362	neutral	None	None	None	None	N
V/D	0.9161	likely_pathogenic	0.9472	pathogenic	-0.696	Destabilizing	0.975	D	0.597	neutral	N	0.346489142	None	None	N
V/E	0.7652	likely_pathogenic	0.8304	pathogenic	-0.778	Destabilizing	0.981	D	0.526	neutral	None	None	None	None	N
V/F	0.4608	ambiguous	0.5261	ambiguous	-0.797	Destabilizing	0.006	N	0.247	neutral	N	0.318222647	None	None	N
V/G	0.7037	likely_pathogenic	0.7569	pathogenic	-1.021	Destabilizing	0.917	D	0.555	neutral	N	0.318997306	None	None	N
V/H	0.9353	likely_pathogenic	0.9564	pathogenic	-0.502	Destabilizing	0.995	D	0.447	neutral	None	None	None	None	N
V/I	0.1078	likely_benign	0.111	benign	-0.448	Destabilizing	0.001	N	0.057	neutral	N	0.348183519	None	None	N
V/K	0.8162	likely_pathogenic	0.8738	pathogenic	-0.84	Destabilizing	0.944	D	0.52	neutral	None	None	None	None	N
V/L	0.3811	ambiguous	0.4079	ambiguous	-0.448	Destabilizing	0.001	N	0.025	neutral	N	0.34602325	None	None	N
V/M	0.3645	ambiguous	0.4077	ambiguous	-0.454	Destabilizing	0.893	D	0.383	neutral	None	None	None	None	N
V/N	0.8162	likely_pathogenic	0.8686	pathogenic	-0.616	Destabilizing	0.981	D	0.588	neutral	None	None	None	None	N
V/P	0.7993	likely_pathogenic	0.8095	pathogenic	-0.539	Destabilizing	0.981	D	0.539	neutral	None	None	None	None	N
V/Q	0.7268	likely_pathogenic	0.7919	pathogenic	-0.852	Destabilizing	0.981	D	0.498	neutral	None	None	None	None	N
V/R	0.7536	likely_pathogenic	0.8242	pathogenic	-0.247	Destabilizing	0.981	D	0.589	neutral	None	None	None	None	N
V/S	0.726	likely_pathogenic	0.7927	pathogenic	-0.996	Destabilizing	0.828	D	0.489	neutral	None	None	None	None	N
V/T	0.5725	likely_pathogenic	0.6464	pathogenic	-0.978	Destabilizing	0.704	D	0.304	neutral	None	None	None	None	N
V/W	0.9638	likely_pathogenic	0.9734	pathogenic	-0.897	Destabilizing	0.995	D	0.452	neutral	None	None	None	None	N
V/Y	0.8731	likely_pathogenic	0.912	pathogenic	-0.625	Destabilizing	0.543	D	0.509	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.