TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17908	53947;53948;53949	chr2:178605573;178605572;178605571	chr2:179470300;179470299;179470298
N2AB	16267	49024;49025;49026	chr2:178605573;178605572;178605571	chr2:179470300;179470299;179470298
N2A	15340	46243;46244;46245	chr2:178605573;178605572;178605571	chr2:179470300;179470299;179470298
N2B	8843	26752;26753;26754	chr2:178605573;178605572;178605571	chr2:179470300;179470299;179470298
Novex-1	8968	27127;27128;27129	chr2:178605573;178605572;178605571	chr2:179470300;179470299;179470298
Novex-2	9035	27328;27329;27330	chr2:178605573;178605572;178605571	chr2:179470300;179470299;179470298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-18
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5776
• 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
D/N	rs778472800	-0.519	0.004	N	0.175	0.107	0.202949470691	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	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
D/A	0.0833	likely_benign	0.0785	benign	-0.272	Destabilizing	0.007	N	0.183	neutral	N	0.454566183	None	None	N
D/C	0.3803	ambiguous	0.3627	ambiguous	-0.3	Destabilizing	0.992	D	0.323	neutral	None	None	None	None	N
D/E	0.0837	likely_benign	0.0902	benign	-0.379	Destabilizing	0.002	N	0.139	neutral	N	0.40858039	None	None	N
D/F	0.3186	likely_benign	0.2969	benign	-0.053	Destabilizing	0.972	D	0.318	neutral	None	None	None	None	N
D/G	0.1173	likely_benign	0.1155	benign	-0.474	Destabilizing	0.201	N	0.283	neutral	N	0.452179239	None	None	N
D/H	0.1599	likely_benign	0.154	benign	0.343	Stabilizing	0.81	D	0.253	neutral	N	0.477251042	None	None	N
D/I	0.1426	likely_benign	0.1235	benign	0.218	Stabilizing	0.92	D	0.345	neutral	None	None	None	None	N
D/K	0.2075	likely_benign	0.2076	benign	0.154	Stabilizing	0.021	N	0.209	neutral	None	None	None	None	N
D/L	0.1862	likely_benign	0.1672	benign	0.218	Stabilizing	0.617	D	0.331	neutral	None	None	None	None	N
D/M	0.2914	likely_benign	0.2909	benign	0.109	Stabilizing	0.992	D	0.311	neutral	None	None	None	None	N
D/N	0.0714	likely_benign	0.0663	benign	-0.272	Destabilizing	0.004	N	0.175	neutral	N	0.473690662	None	None	N
D/P	0.5213	ambiguous	0.5141	ambiguous	0.076	Stabilizing	0.92	D	0.305	neutral	None	None	None	None	N
D/Q	0.1574	likely_benign	0.1647	benign	-0.219	Destabilizing	0.447	N	0.227	neutral	None	None	None	None	N
D/R	0.2456	likely_benign	0.2528	benign	0.497	Stabilizing	0.447	N	0.303	neutral	None	None	None	None	N
D/S	0.0801	likely_benign	0.0799	benign	-0.366	Destabilizing	0.25	N	0.24	neutral	None	None	None	None	N
D/T	0.1034	likely_benign	0.1022	benign	-0.202	Destabilizing	0.617	D	0.264	neutral	None	None	None	None	N
D/V	0.0961	likely_benign	0.0828	benign	0.076	Stabilizing	0.549	D	0.326	neutral	N	0.469170276	None	None	N
D/W	0.7252	likely_pathogenic	0.7252	pathogenic	0.107	Stabilizing	0.992	D	0.417	neutral	None	None	None	None	N
D/Y	0.1707	likely_benign	0.1529	benign	0.187	Stabilizing	0.963	D	0.318	neutral	N	0.521137892	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.