TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9142	27649;27650;27651	chr2:178712498;178712497;178712496	chr2:179577225;179577224;179577223
N2AB	8825	26698;26699;26700	chr2:178712498;178712497;178712496	chr2:179577225;179577224;179577223
N2A	7898	23917;23918;23919	chr2:178712498;178712497;178712496	chr2:179577225;179577224;179577223
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCG
• RefSeq wild type template codon: AGC
• Domain: Ig-77
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.338
• 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
S/L	rs781609380	0.083	0.009	D	0.309	0.212	0.21737058555	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
S/L	rs781609380	0.083	0.009	D	0.309	0.212	0.21737058555	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.78011E-04
S/L	rs781609380	0.083	0.009	D	0.309	0.212	0.21737058555	gnomAD-4.0.0	1.17748E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18666E-05	4.39184E-05	1.60113E-05

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	0.0635	likely_benign	0.0661	benign	-0.312	Destabilizing	0.101	N	0.291	neutral	N	0.500083121	None	None	N
S/C	0.1459	likely_benign	0.126	benign	-0.427	Destabilizing	0.951	D	0.469	neutral	None	None	None	None	N
S/D	0.2658	likely_benign	0.2747	benign	0.054	Stabilizing	0.264	N	0.325	neutral	None	None	None	None	N
S/E	0.3081	likely_benign	0.3478	ambiguous	0.006	Stabilizing	0.418	N	0.323	neutral	None	None	None	None	N
S/F	0.1114	likely_benign	0.108	benign	-0.723	Destabilizing	0.002	N	0.343	neutral	None	None	None	None	N
S/G	0.1435	likely_benign	0.1276	benign	-0.492	Destabilizing	0.228	N	0.333	neutral	None	None	None	None	N
S/H	0.2044	likely_benign	0.2129	benign	-0.979	Destabilizing	0.836	D	0.496	neutral	None	None	None	None	N
S/I	0.1072	likely_benign	0.1056	benign	0.037	Stabilizing	0.264	N	0.493	neutral	None	None	None	None	N
S/K	0.3647	ambiguous	0.4094	ambiguous	-0.58	Destabilizing	0.418	N	0.32	neutral	None	None	None	None	N
S/L	0.0676	likely_benign	0.0697	benign	0.037	Stabilizing	0.009	N	0.309	neutral	D	0.537409358	None	None	N
S/M	0.139	likely_benign	0.1295	benign	0.049	Stabilizing	0.716	D	0.499	neutral	None	None	None	None	N
S/N	0.1321	likely_benign	0.1158	benign	-0.454	Destabilizing	0.01	N	0.183	neutral	None	None	None	None	N
S/P	0.6026	likely_pathogenic	0.6009	pathogenic	-0.047	Destabilizing	0.794	D	0.523	neutral	N	0.513386279	None	None	N
S/Q	0.3014	likely_benign	0.3228	benign	-0.595	Destabilizing	0.836	D	0.465	neutral	None	None	None	None	N
S/R	0.3149	likely_benign	0.3493	ambiguous	-0.439	Destabilizing	0.716	D	0.525	neutral	None	None	None	None	N
S/T	0.0668	likely_benign	0.0654	benign	-0.46	Destabilizing	None	N	0.107	neutral	N	0.466623908	None	None	N
S/V	0.1095	likely_benign	0.1092	benign	-0.047	Destabilizing	0.129	N	0.455	neutral	None	None	None	None	N
S/W	0.2259	likely_benign	0.2415	benign	-0.77	Destabilizing	0.991	D	0.588	neutral	N	0.513893258	None	None	N
S/Y	0.1203	likely_benign	0.1236	benign	-0.468	Destabilizing	0.557	D	0.567	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.