TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20325	61198;61199;61200	chr2:178590752;178590751;178590750	chr2:179455479;179455478;179455477
N2AB	18684	56275;56276;56277	chr2:178590752;178590751;178590750	chr2:179455479;179455478;179455477
N2A	17757	53494;53495;53496	chr2:178590752;178590751;178590750	chr2:179455479;179455478;179455477
N2B	11260	34003;34004;34005	chr2:178590752;178590751;178590750	chr2:179455479;179455478;179455477
Novex-1	11385	34378;34379;34380	chr2:178590752;178590751;178590750	chr2:179455479;179455478;179455477
Novex-2	11452	34579;34580;34581	chr2:178590752;178590751;178590750	chr2:179455479;179455478;179455477
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-35
• Domain position: 55
• Structural Position: 77
• Q(SASA): 0.1416
• 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
I/T	None	None	None	N	0.217	0.12	0.442567846599	gnomAD-4.0.0	3.42888E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.81883E-05	0
I/V	rs372353944	None	None	N	0.125	0.051	0.141422826196	gnomAD-4.0.0	1.59991E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87733E-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
I/A	0.2705	likely_benign	0.3113	benign	-1.878	Destabilizing	0.007	N	0.281	neutral	None	None	None	None	N
I/C	0.6223	likely_pathogenic	0.5961	pathogenic	-0.908	Destabilizing	None	N	0.218	neutral	None	None	None	None	N
I/D	0.9312	likely_pathogenic	0.9259	pathogenic	-2.064	Highly Destabilizing	0.072	N	0.513	neutral	None	None	None	None	N
I/E	0.847	likely_pathogenic	0.8338	pathogenic	-1.792	Destabilizing	0.072	N	0.515	neutral	None	None	None	None	N
I/F	0.2962	likely_benign	0.3472	ambiguous	-1.033	Destabilizing	0.029	N	0.417	neutral	N	0.470279148	None	None	N
I/G	0.7566	likely_pathogenic	0.7818	pathogenic	-2.446	Highly Destabilizing	0.072	N	0.453	neutral	None	None	None	None	N
I/H	0.7977	likely_pathogenic	0.7898	pathogenic	-2.107	Highly Destabilizing	0.864	D	0.483	neutral	None	None	None	None	N
I/K	0.7733	likely_pathogenic	0.7414	pathogenic	-1.149	Destabilizing	0.072	N	0.479	neutral	None	None	None	None	N
I/L	0.0929	likely_benign	0.0995	benign	-0.227	Destabilizing	None	N	0.103	neutral	N	0.51315034	None	None	N
I/M	0.1082	likely_benign	0.1191	benign	-0.199	Destabilizing	0.208	N	0.452	neutral	N	0.491675085	None	None	N
I/N	0.5967	likely_pathogenic	0.5331	ambiguous	-1.61	Destabilizing	0.171	N	0.545	neutral	N	0.463843459	None	None	N
I/P	0.8816	likely_pathogenic	0.9083	pathogenic	-0.759	Destabilizing	0.356	N	0.551	neutral	None	None	None	None	N
I/Q	0.7083	likely_pathogenic	0.697	pathogenic	-1.347	Destabilizing	0.356	N	0.511	neutral	None	None	None	None	N
I/R	0.6862	likely_pathogenic	0.6575	pathogenic	-1.216	Destabilizing	0.214	N	0.539	neutral	None	None	None	None	N
I/S	0.4348	ambiguous	0.4143	ambiguous	-2.273	Highly Destabilizing	0.012	N	0.382	neutral	N	0.51414763	None	None	N
I/T	0.2234	likely_benign	0.2395	benign	-1.842	Destabilizing	None	N	0.217	neutral	N	0.498658103	None	None	N
I/V	0.0618	likely_benign	0.0649	benign	-0.759	Destabilizing	None	N	0.125	neutral	N	0.411735339	None	None	N
I/W	0.8987	likely_pathogenic	0.9254	pathogenic	-1.471	Destabilizing	0.864	D	0.509	neutral	None	None	None	None	N
I/Y	0.7702	likely_pathogenic	0.7923	pathogenic	-1.071	Destabilizing	0.356	N	0.528	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.