TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24974	75145;75146;75147	chr2:178571212;178571211;178571210	chr2:179435939;179435938;179435937
N2AB	23333	70222;70223;70224	chr2:178571212;178571211;178571210	chr2:179435939;179435938;179435937
N2A	22406	67441;67442;67443	chr2:178571212;178571211;178571210	chr2:179435939;179435938;179435937
N2B	15909	47950;47951;47952	chr2:178571212;178571211;178571210	chr2:179435939;179435938;179435937
Novex-1	16034	48325;48326;48327	chr2:178571212;178571211;178571210	chr2:179435939;179435938;179435937
Novex-2	16101	48526;48527;48528	chr2:178571212;178571211;178571210	chr2:179435939;179435938;179435937
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-69
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.5898
• 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
E/A	rs933954403	None	0.22	D	0.507	0.18	None	gnomAD-4.0.0	3.18354E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85925E-06	0	3.02517E-05
E/K	rs372061666	0.333	0.22	N	0.513	0.127	None	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
E/K	rs372061666	0.333	0.22	N	0.513	0.127	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs372061666	0.333	0.22	N	0.513	0.127	None	gnomAD-4.0.0	2.56302E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78776E-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
E/A	0.233	likely_benign	0.229	benign	-0.623	Destabilizing	0.22	N	0.507	neutral	D	0.523503406	None	None	N
E/C	0.8387	likely_pathogenic	0.8212	pathogenic	-0.331	Destabilizing	0.968	D	0.691	prob.neutral	None	None	None	None	N
E/D	0.1192	likely_benign	0.1083	benign	-0.717	Destabilizing	None	N	0.138	neutral	N	0.470786429	None	None	N
E/F	0.8013	likely_pathogenic	0.7852	pathogenic	0.086	Stabilizing	0.396	N	0.634	neutral	None	None	None	None	N
E/G	0.2785	likely_benign	0.2696	benign	-0.948	Destabilizing	0.22	N	0.491	neutral	N	0.511935842	None	None	N
E/H	0.5788	likely_pathogenic	0.5405	ambiguous	0.249	Stabilizing	0.567	D	0.506	neutral	None	None	None	None	N
E/I	0.3819	ambiguous	0.3634	ambiguous	0.252	Stabilizing	0.567	D	0.634	neutral	None	None	None	None	N
E/K	0.285	likely_benign	0.2649	benign	0.074	Stabilizing	0.22	N	0.513	neutral	N	0.456142264	None	None	N
E/L	0.4088	ambiguous	0.4016	ambiguous	0.252	Stabilizing	0.396	N	0.543	neutral	None	None	None	None	N
E/M	0.5008	ambiguous	0.4862	ambiguous	0.404	Stabilizing	0.968	D	0.603	neutral	None	None	None	None	N
E/N	0.3093	likely_benign	0.2863	benign	-0.666	Destabilizing	0.396	N	0.466	neutral	None	None	None	None	N
E/P	0.7921	likely_pathogenic	0.7881	pathogenic	-0.019	Destabilizing	0.726	D	0.571	neutral	None	None	None	None	N
E/Q	0.2031	likely_benign	0.1935	benign	-0.531	Destabilizing	0.497	N	0.472	neutral	N	0.458971925	None	None	N
E/R	0.3925	ambiguous	0.3663	ambiguous	0.467	Stabilizing	0.567	D	0.521	neutral	None	None	None	None	N
E/S	0.2632	likely_benign	0.2455	benign	-0.864	Destabilizing	0.157	N	0.493	neutral	None	None	None	None	N
E/T	0.2619	likely_benign	0.2512	benign	-0.574	Destabilizing	0.567	D	0.49	neutral	None	None	None	None	N
E/V	0.228	likely_benign	0.2251	benign	-0.019	Destabilizing	0.497	N	0.515	neutral	N	0.498626392	None	None	N
E/W	0.9141	likely_pathogenic	0.902	pathogenic	0.435	Stabilizing	0.909	D	0.663	neutral	None	None	None	None	N
E/Y	0.6822	likely_pathogenic	0.6629	pathogenic	0.395	Stabilizing	0.003	N	0.432	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.