TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7973	24142;24143;24144	chr2:178719575;178719574;178719573	chr2:179584302;179584301;179584300
N2AB	7656	23191;23192;23193	chr2:178719575;178719574;178719573	chr2:179584302;179584301;179584300
N2A	6729	20410;20411;20412	chr2:178719575;178719574;178719573	chr2:179584302;179584301;179584300
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-64
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.5137
• 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/A	None	None	0.027	D	0.441	0.121	0.190952846119	gnomAD-4.0.0	1.59876E-06	None	None	None	None	N	None	0	0	None	0	2.77546E-05	None	0	0	0	0	0
T/I	rs768738299	0.054	0.317	N	0.657	0.336	0.459906663326	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
T/I	rs768738299	0.054	0.317	N	0.657	0.336	0.459906663326	gnomAD-4.0.0	1.59921E-06	None	None	None	None	N	None	5.66829E-05	0	None	0	0	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
T/A	0.0782	likely_benign	0.0813	benign	-0.523	Destabilizing	0.027	N	0.441	neutral	D	0.524554704	None	None	N
T/C	0.394	ambiguous	0.4406	ambiguous	-0.281	Destabilizing	0.824	D	0.596	neutral	None	None	None	None	N
T/D	0.2795	likely_benign	0.3037	benign	0.193	Stabilizing	0.081	N	0.55	neutral	None	None	None	None	N
T/E	0.2374	likely_benign	0.2458	benign	0.138	Stabilizing	0.035	N	0.504	neutral	None	None	None	None	N
T/F	0.1918	likely_benign	0.2153	benign	-0.924	Destabilizing	0.555	D	0.655	neutral	None	None	None	None	N
T/G	0.26	likely_benign	0.2803	benign	-0.691	Destabilizing	0.035	N	0.551	neutral	None	None	None	None	N
T/H	0.2049	likely_benign	0.2225	benign	-0.995	Destabilizing	0.001	N	0.503	neutral	None	None	None	None	N
T/I	0.1479	likely_benign	0.1666	benign	-0.195	Destabilizing	0.317	N	0.657	neutral	N	0.488481168	None	None	N
T/K	0.1769	likely_benign	0.1849	benign	-0.424	Destabilizing	0.001	N	0.319	neutral	None	None	None	None	N
T/L	0.0999	likely_benign	0.1106	benign	-0.195	Destabilizing	0.149	N	0.543	neutral	None	None	None	None	N
T/M	0.0853	likely_benign	0.0875	benign	0.013	Stabilizing	0.791	D	0.614	neutral	None	None	None	None	N
T/N	0.1166	likely_benign	0.123	benign	-0.219	Destabilizing	0.002	N	0.257	neutral	N	0.492493639	None	None	N
T/P	0.1824	likely_benign	0.1939	benign	-0.274	Destabilizing	0.317	N	0.639	neutral	N	0.491786077	None	None	N
T/Q	0.1953	likely_benign	0.1998	benign	-0.42	Destabilizing	0.149	N	0.64	neutral	None	None	None	None	N
T/R	0.1325	likely_benign	0.1293	benign	-0.176	Destabilizing	0.081	N	0.567	neutral	None	None	None	None	N
T/S	0.0915	likely_benign	0.0936	benign	-0.463	Destabilizing	None	N	0.243	neutral	N	0.478992986	None	None	N
T/V	0.1216	likely_benign	0.1348	benign	-0.274	Destabilizing	0.149	N	0.519	neutral	None	None	None	None	N
T/W	0.4969	ambiguous	0.5278	ambiguous	-0.901	Destabilizing	0.935	D	0.64	neutral	None	None	None	None	N
T/Y	0.2344	likely_benign	0.2648	benign	-0.632	Destabilizing	0.38	N	0.675	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.