TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24581	73966;73967;73968	chr2:178572391;178572390;178572389	chr2:179437118;179437117;179437116
N2AB	22940	69043;69044;69045	chr2:178572391;178572390;178572389	chr2:179437118;179437117;179437116
N2A	22013	66262;66263;66264	chr2:178572391;178572390;178572389	chr2:179437118;179437117;179437116
N2B	15516	46771;46772;46773	chr2:178572391;178572390;178572389	chr2:179437118;179437117;179437116
Novex-1	15641	47146;47147;47148	chr2:178572391;178572390;178572389	chr2:179437118;179437117;179437116
Novex-2	15708	47347;47348;47349	chr2:178572391;178572390;178572389	chr2:179437118;179437117;179437116
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: Fn3-66
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.366
• 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/A	None	None	0.035	N	0.486	0.138	0.266385636622	gnomAD-4.0.0	6.84517E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99845E-07	0	0
D/E	rs727504603	None	None	N	0.132	0.076	0.115124310173	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/E	rs727504603	None	None	N	0.132	0.076	0.115124310173	gnomAD-4.0.0	2.46432E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.87322E-05	0	3.14953E-05	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	0.1913	likely_benign	0.1797	benign	-0.395	Destabilizing	0.035	N	0.486	neutral	N	0.498066244	None	None	N
D/C	0.574	likely_pathogenic	0.5413	ambiguous	-0.043	Destabilizing	0.846	D	0.607	neutral	None	None	None	None	N
D/E	0.0926	likely_benign	0.0992	benign	-0.439	Destabilizing	None	N	0.132	neutral	N	0.429705024	None	None	N
D/F	0.6431	likely_pathogenic	0.5886	pathogenic	-0.181	Destabilizing	0.948	D	0.587	neutral	None	None	None	None	N
D/G	0.1826	likely_benign	0.1712	benign	-0.652	Destabilizing	None	N	0.196	neutral	N	0.476768252	None	None	N
D/H	0.3654	ambiguous	0.342	ambiguous	-0.217	Destabilizing	0.627	D	0.527	neutral	N	0.516190645	None	None	N
D/I	0.3675	ambiguous	0.3433	ambiguous	0.252	Stabilizing	0.856	D	0.602	neutral	None	None	None	None	N
D/K	0.4439	ambiguous	0.4612	ambiguous	0.11	Stabilizing	0.296	N	0.44	neutral	None	None	None	None	N
D/L	0.3516	ambiguous	0.3265	benign	0.252	Stabilizing	0.746	D	0.577	neutral	None	None	None	None	N
D/M	0.5488	ambiguous	0.5101	ambiguous	0.493	Stabilizing	0.962	D	0.587	neutral	None	None	None	None	N
D/N	0.1291	likely_benign	0.1226	benign	-0.275	Destabilizing	None	N	0.287	neutral	N	0.476632179	None	None	N
D/P	0.4573	ambiguous	0.4699	ambiguous	0.06	Stabilizing	0.106	N	0.545	neutral	None	None	None	None	N
D/Q	0.3153	likely_benign	0.3053	benign	-0.205	Destabilizing	0.355	N	0.461	neutral	None	None	None	None	N
D/R	0.528	ambiguous	0.5371	ambiguous	0.284	Stabilizing	0.746	D	0.582	neutral	None	None	None	None	N
D/S	0.1261	likely_benign	0.1188	benign	-0.412	Destabilizing	0.046	N	0.405	neutral	None	None	None	None	N
D/T	0.2062	likely_benign	0.1889	benign	-0.206	Destabilizing	0.094	N	0.49	neutral	None	None	None	None	N
D/V	0.2403	likely_benign	0.2225	benign	0.06	Stabilizing	0.28	N	0.577	neutral	N	0.483251507	None	None	N
D/W	0.898	likely_pathogenic	0.8871	pathogenic	-0.004	Destabilizing	0.986	D	0.611	neutral	None	None	None	None	N
D/Y	0.3439	ambiguous	0.3234	benign	0.066	Stabilizing	0.932	D	0.587	neutral	N	0.478863976	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.