TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29580	88963;88964;88965	chr2:178554609;178554608;178554607	chr2:179419336;179419335;179419334
N2AB	27939	84040;84041;84042	chr2:178554609;178554608;178554607	chr2:179419336;179419335;179419334
N2A	27012	81259;81260;81261	chr2:178554609;178554608;178554607	chr2:179419336;179419335;179419334
N2B	20515	61768;61769;61770	chr2:178554609;178554608;178554607	chr2:179419336;179419335;179419334
Novex-1	20640	62143;62144;62145	chr2:178554609;178554608;178554607	chr2:179419336;179419335;179419334
Novex-2	20707	62344;62345;62346	chr2:178554609;178554608;178554607	chr2:179419336;179419335;179419334
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-103
• Domain position: 48
• Structural Position: 64
• Q(SASA): 0.6524
• 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
V/L	rs371096025	-0.103	0.509	N	0.267	0.167	0.5763749866	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	9.95E-05	0	None	0	None	0	0	0
V/L	rs371096025	-0.103	0.509	N	0.267	0.167	0.5763749866	gnomAD-4.0.0	1.59102E-06	None	None	None	None	I	None	0	0	None	4.76644E-05	0	None	0	0	0	0	0
V/M	None	-0.413	0.31	N	0.228	0.153	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	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	0.3259	likely_benign	0.3447	ambiguous	-0.683	Destabilizing	0.134	N	0.179	neutral	N	0.446829347	None	None	I
V/C	0.8443	likely_pathogenic	0.8484	pathogenic	-0.676	Destabilizing	0.999	D	0.327	neutral	None	None	None	None	I
V/D	0.8225	likely_pathogenic	0.8433	pathogenic	-0.472	Destabilizing	0.991	D	0.44	neutral	None	None	None	None	I
V/E	0.7249	likely_pathogenic	0.7593	pathogenic	-0.548	Destabilizing	0.988	D	0.349	neutral	N	0.430742387	None	None	I
V/F	0.2979	likely_benign	0.3336	benign	-0.697	Destabilizing	0.982	D	0.313	neutral	None	None	None	None	I
V/G	0.4504	ambiguous	0.4699	ambiguous	-0.861	Destabilizing	0.92	D	0.386	neutral	N	0.43788179	None	None	I
V/H	0.8449	likely_pathogenic	0.863	pathogenic	-0.304	Destabilizing	0.999	D	0.461	neutral	None	None	None	None	I
V/I	0.0993	likely_benign	0.1027	benign	-0.342	Destabilizing	0.759	D	0.375	neutral	None	None	None	None	I
V/K	0.8005	likely_pathogenic	0.8258	pathogenic	-0.638	Destabilizing	0.969	D	0.36	neutral	None	None	None	None	I
V/L	0.2881	likely_benign	0.3242	benign	-0.342	Destabilizing	0.509	D	0.267	neutral	N	0.409831184	None	None	I
V/M	0.2223	likely_benign	0.2568	benign	-0.476	Destabilizing	0.31	N	0.228	neutral	N	0.476229535	None	None	I
V/N	0.5333	ambiguous	0.5593	ambiguous	-0.411	Destabilizing	0.997	D	0.437	neutral	None	None	None	None	I
V/P	0.8644	likely_pathogenic	0.8782	pathogenic	-0.42	Destabilizing	0.991	D	0.402	neutral	None	None	None	None	I
V/Q	0.6257	likely_pathogenic	0.6581	pathogenic	-0.62	Destabilizing	0.991	D	0.412	neutral	None	None	None	None	I
V/R	0.7365	likely_pathogenic	0.7576	pathogenic	-0.1	Destabilizing	0.991	D	0.442	neutral	None	None	None	None	I
V/S	0.3882	ambiguous	0.4038	ambiguous	-0.793	Destabilizing	0.884	D	0.326	neutral	None	None	None	None	I
V/T	0.373	ambiguous	0.3972	ambiguous	-0.766	Destabilizing	0.939	D	0.297	neutral	None	None	None	None	I
V/W	0.9435	likely_pathogenic	0.9526	pathogenic	-0.794	Destabilizing	0.999	D	0.499	neutral	None	None	None	None	I
V/Y	0.8025	likely_pathogenic	0.8147	pathogenic	-0.509	Destabilizing	0.997	D	0.3	neutral	None	None	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.