TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16476	49651;49652;49653	chr2:178613857;178613856;178613855	chr2:179478584;179478583;179478582
N2AB	14835	44728;44729;44730	chr2:178613857;178613856;178613855	chr2:179478584;179478583;179478582
N2A	13908	41947;41948;41949	chr2:178613857;178613856;178613855	chr2:179478584;179478583;179478582
N2B	7411	22456;22457;22458	chr2:178613857;178613856;178613855	chr2:179478584;179478583;179478582
Novex-1	7536	22831;22832;22833	chr2:178613857;178613856;178613855	chr2:179478584;179478583;179478582
Novex-2	7603	23032;23033;23034	chr2:178613857;178613856;178613855	chr2:179478584;179478583;179478582
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-7
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4634
• 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
D/E	None	None	0.02	N	0.179	0.032	0.134241683229	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
D/N	None	None	0.939	N	0.478	0.299	0.281381271821	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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
D/A	0.2464	likely_benign	0.2235	benign	-0.152	Destabilizing	0.939	D	0.499	neutral	N	0.475525593	None	None	I
D/C	0.6396	likely_pathogenic	0.5988	pathogenic	0.317	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
D/E	0.1534	likely_benign	0.1352	benign	-0.308	Destabilizing	0.02	N	0.179	neutral	N	0.459006083	None	None	I
D/F	0.5887	likely_pathogenic	0.5484	ambiguous	-0.382	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	I
D/G	0.3413	ambiguous	0.3139	benign	-0.326	Destabilizing	0.939	D	0.489	neutral	N	0.468645562	None	None	I
D/H	0.3371	likely_benign	0.3025	benign	-0.407	Destabilizing	0.998	D	0.503	neutral	N	0.473429401	None	None	I
D/I	0.3856	ambiguous	0.351	ambiguous	0.247	Stabilizing	0.993	D	0.701	prob.neutral	None	None	None	None	I
D/K	0.4515	ambiguous	0.4132	ambiguous	0.402	Stabilizing	0.91	D	0.463	neutral	None	None	None	None	I
D/L	0.4569	ambiguous	0.4122	ambiguous	0.247	Stabilizing	0.986	D	0.683	prob.neutral	None	None	None	None	I
D/M	0.608	likely_pathogenic	0.5681	pathogenic	0.514	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
D/N	0.1224	likely_benign	0.1152	benign	0.272	Stabilizing	0.939	D	0.478	neutral	N	0.471925356	None	None	I
D/P	0.9653	likely_pathogenic	0.9649	pathogenic	0.136	Stabilizing	0.993	D	0.513	neutral	None	None	None	None	I
D/Q	0.395	ambiguous	0.3406	ambiguous	0.279	Stabilizing	0.973	D	0.455	neutral	None	None	None	None	I
D/R	0.5042	ambiguous	0.4582	ambiguous	0.392	Stabilizing	0.986	D	0.619	neutral	None	None	None	None	I
D/S	0.1432	likely_benign	0.1312	benign	0.169	Stabilizing	0.953	D	0.407	neutral	None	None	None	None	I
D/T	0.248	likely_benign	0.2185	benign	0.295	Stabilizing	0.986	D	0.469	neutral	None	None	None	None	I
D/V	0.2476	likely_benign	0.2209	benign	0.136	Stabilizing	0.991	D	0.677	prob.neutral	N	0.467182752	None	None	I
D/W	0.8839	likely_pathogenic	0.8699	pathogenic	-0.36	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
D/Y	0.2412	likely_benign	0.2259	benign	-0.171	Destabilizing	0.997	D	0.677	prob.neutral	N	0.434756384	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.