TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30052	90379;90380;90381	chr2:178552746;178552745;178552744	chr2:179417473;179417472;179417471
N2AB	28411	85456;85457;85458	chr2:178552746;178552745;178552744	chr2:179417473;179417472;179417471
N2A	27484	82675;82676;82677	chr2:178552746;178552745;178552744	chr2:179417473;179417472;179417471
N2B	20987	63184;63185;63186	chr2:178552746;178552745;178552744	chr2:179417473;179417472;179417471
Novex-1	21112	63559;63560;63561	chr2:178552746;178552745;178552744	chr2:179417473;179417472;179417471
Novex-2	21179	63760;63761;63762	chr2:178552746;178552745;178552744	chr2:179417473;179417472;179417471
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-107
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4928
• 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
T/N	None	None	None	N	0.275	0.121	0.193865811164	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
T/A	0.0784	likely_benign	0.0755	benign	-0.884	Destabilizing	0.027	N	0.361	neutral	N	0.495836802	None	None	N
T/C	0.3174	likely_benign	0.3009	benign	-0.507	Destabilizing	0.824	D	0.503	neutral	None	None	None	None	N
T/D	0.3729	ambiguous	0.3431	ambiguous	-0.813	Destabilizing	0.081	N	0.465	neutral	None	None	None	None	N
T/E	0.2456	likely_benign	0.2364	benign	-0.739	Destabilizing	0.081	N	0.466	neutral	None	None	None	None	N
T/F	0.266	likely_benign	0.2402	benign	-0.632	Destabilizing	0.38	N	0.606	neutral	None	None	None	None	N
T/G	0.1691	likely_benign	0.1598	benign	-1.228	Destabilizing	0.081	N	0.499	neutral	None	None	None	None	N
T/H	0.227	likely_benign	0.2066	benign	-1.475	Destabilizing	0.38	N	0.567	neutral	None	None	None	None	N
T/I	0.1683	likely_benign	0.1658	benign	-0.029	Destabilizing	0.062	N	0.53	neutral	N	0.505515078	None	None	N
T/K	0.1569	likely_benign	0.1512	benign	-1.009	Destabilizing	0.081	N	0.464	neutral	None	None	None	None	N
T/L	0.0859	likely_benign	0.0823	benign	-0.029	Destabilizing	0.001	N	0.289	neutral	None	None	None	None	N
T/M	0.0845	likely_benign	0.0812	benign	0.183	Stabilizing	0.38	N	0.529	neutral	None	None	None	None	N
T/N	0.0913	likely_benign	0.0844	benign	-1.158	Destabilizing	None	N	0.275	neutral	N	0.477539043	None	None	N
T/P	0.2539	likely_benign	0.2286	benign	-0.281	Destabilizing	0.484	N	0.573	neutral	N	0.47046064	None	None	N
T/Q	0.1638	likely_benign	0.1546	benign	-1.132	Destabilizing	0.38	N	0.569	neutral	None	None	None	None	N
T/R	0.146	likely_benign	0.1335	benign	-0.898	Destabilizing	0.38	N	0.57	neutral	None	None	None	None	N
T/S	0.091	likely_benign	0.089	benign	-1.355	Destabilizing	None	N	0.149	neutral	N	0.450947088	None	None	N
T/V	0.1308	likely_benign	0.13	benign	-0.281	Destabilizing	0.081	N	0.361	neutral	None	None	None	None	N
T/W	0.5671	likely_pathogenic	0.5249	ambiguous	-0.703	Destabilizing	0.935	D	0.611	neutral	None	None	None	None	N
T/Y	0.2761	likely_benign	0.2511	benign	-0.456	Destabilizing	0.555	D	0.599	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.