TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7214	21865;21866;21867	chr2:178723460;178723459;178723458	chr2:179588187;179588186;179588185
N2AB	6897	20914;20915;20916	chr2:178723460;178723459;178723458	chr2:179588187;179588186;179588185
N2A	5970	18133;18134;18135	chr2:178723460;178723459;178723458	chr2:179588187;179588186;179588185
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-56
• Domain position: 78
• Structural Position: 162
• Q(SASA): 1.0621
• Predicted PPI site: I

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
N/D	rs998292768	None	None	N	0.093	0.25	0.0401082797425	gnomAD-4.0.0	3.18527E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72007E-06	0	0
N/S	rs755600935	0.258	0.005	N	0.178	0.1	0.117506650769	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.47E-05	0	None	0	0	None	0	None	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
N/A	0.1019	likely_benign	0.1045	benign	-0.137	Destabilizing	None	N	0.104	neutral	None	None	None	None	I
N/C	0.2298	likely_benign	0.256	benign	0.231	Stabilizing	0.864	D	0.179	neutral	None	None	None	None	I
N/D	0.0513	likely_benign	0.0565	benign	-0.029	Destabilizing	None	N	0.093	neutral	N	0.354453196	None	None	I
N/E	0.1101	likely_benign	0.1088	benign	-0.1	Destabilizing	None	N	0.128	neutral	None	None	None	None	I
N/F	0.3217	likely_benign	0.337	benign	-0.748	Destabilizing	0.628	D	0.233	neutral	None	None	None	None	I
N/G	0.1436	likely_benign	0.1545	benign	-0.217	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
N/H	0.0849	likely_benign	0.0846	benign	-0.296	Destabilizing	0.295	N	0.205	neutral	N	0.473029806	None	None	I
N/I	0.1176	likely_benign	0.1173	benign	-0.026	Destabilizing	0.106	N	0.255	neutral	N	0.452385175	None	None	I
N/K	0.1297	likely_benign	0.1234	benign	0.104	Stabilizing	None	N	0.141	neutral	N	0.424350424	None	None	I
N/L	0.1458	likely_benign	0.145	benign	-0.026	Destabilizing	0.031	N	0.235	neutral	None	None	None	None	I
N/M	0.2251	likely_benign	0.2247	benign	0.16	Stabilizing	0.628	D	0.219	neutral	None	None	None	None	I
N/P	0.2939	likely_benign	0.2988	benign	-0.041	Destabilizing	0.136	N	0.344	neutral	None	None	None	None	I
N/Q	0.1566	likely_benign	0.1527	benign	-0.22	Destabilizing	0.038	N	0.247	neutral	None	None	None	None	I
N/R	0.1483	likely_benign	0.1466	benign	0.172	Stabilizing	0.038	N	0.243	neutral	None	None	None	None	I
N/S	0.0653	likely_benign	0.0649	benign	0.032	Stabilizing	0.005	N	0.178	neutral	N	0.413477283	None	None	I
N/T	0.0912	likely_benign	0.0901	benign	0.063	Stabilizing	0.024	N	0.219	neutral	N	0.443610976	None	None	I
N/V	0.114	likely_benign	0.1144	benign	-0.041	Destabilizing	0.031	N	0.239	neutral	None	None	None	None	I
N/W	0.5583	ambiguous	0.5814	pathogenic	-0.878	Destabilizing	0.864	D	0.187	neutral	None	None	None	None	I
N/Y	0.1122	likely_benign	0.118	benign	-0.561	Destabilizing	0.56	D	0.249	neutral	N	0.473029806	None	None	I

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.