TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28576	85951;85952;85953	chr2:178560406;178560405;178560404	chr2:179425133;179425132;179425131
N2AB	26935	81028;81029;81030	chr2:178560406;178560405;178560404	chr2:179425133;179425132;179425131
N2A	26008	78247;78248;78249	chr2:178560406;178560405;178560404	chr2:179425133;179425132;179425131
N2B	19511	58756;58757;58758	chr2:178560406;178560405;178560404	chr2:179425133;179425132;179425131
Novex-1	19636	59131;59132;59133	chr2:178560406;178560405;178560404	chr2:179425133;179425132;179425131
Novex-2	19703	59332;59333;59334	chr2:178560406;178560405;178560404	chr2:179425133;179425132;179425131
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-96
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.3705
• 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
S/R	rs1313703882	None	0.497	N	0.528	0.112	0.218112801441	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

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
S/A	0.1121	likely_benign	0.1032	benign	-0.54	Destabilizing	0.072	N	0.502	neutral	None	None	None	None	I
S/C	0.1326	likely_benign	0.1223	benign	-0.278	Destabilizing	0.883	D	0.553	neutral	N	0.472592871	None	None	I
S/D	0.2188	likely_benign	0.2045	benign	-0.15	Destabilizing	0.157	N	0.46	neutral	None	None	None	None	I
S/E	0.3652	ambiguous	0.324	benign	-0.245	Destabilizing	0.272	N	0.469	neutral	None	None	None	None	I
S/F	0.1979	likely_benign	0.1781	benign	-1.177	Destabilizing	0.726	D	0.684	prob.neutral	None	None	None	None	I
S/G	0.1065	likely_benign	0.1004	benign	-0.648	Destabilizing	0.124	N	0.464	neutral	N	0.467971289	None	None	I
S/H	0.2513	likely_benign	0.2325	benign	-1.257	Destabilizing	0.832	D	0.526	neutral	None	None	None	None	I
S/I	0.1938	likely_benign	0.1726	benign	-0.379	Destabilizing	0.331	N	0.68	prob.neutral	N	0.469692809	None	None	I
S/K	0.4743	ambiguous	0.4265	ambiguous	-0.558	Destabilizing	0.157	N	0.471	neutral	None	None	None	None	I
S/L	0.1298	likely_benign	0.1138	benign	-0.379	Destabilizing	0.157	N	0.591	neutral	None	None	None	None	I
S/M	0.1757	likely_benign	0.1609	benign	0.091	Stabilizing	0.909	D	0.527	neutral	None	None	None	None	I
S/N	0.0895	likely_benign	0.087	benign	-0.301	Destabilizing	0.001	N	0.261	neutral	N	0.463969526	None	None	I
S/P	0.8138	likely_pathogenic	0.7678	pathogenic	-0.405	Destabilizing	0.726	D	0.529	neutral	None	None	None	None	I
S/Q	0.4059	ambiguous	0.3642	ambiguous	-0.615	Destabilizing	0.567	D	0.47	neutral	None	None	None	None	I
S/R	0.4645	ambiguous	0.4195	ambiguous	-0.329	Destabilizing	0.497	N	0.528	neutral	N	0.519073448	None	None	I
S/T	0.0793	likely_benign	0.0785	benign	-0.395	Destabilizing	0.001	N	0.211	neutral	N	0.488731898	None	None	I
S/V	0.2034	likely_benign	0.1791	benign	-0.405	Destabilizing	0.396	N	0.596	neutral	None	None	None	None	I
S/W	0.3383	likely_benign	0.3001	benign	-1.152	Destabilizing	0.968	D	0.721	prob.delet.	None	None	None	None	I
S/Y	0.1566	likely_benign	0.1438	benign	-0.885	Destabilizing	0.726	D	0.669	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.