TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28836	86731;86732;86733	chr2:178559626;178559625;178559624	chr2:179424353;179424352;179424351
N2AB	27195	81808;81809;81810	chr2:178559626;178559625;178559624	chr2:179424353;179424352;179424351
N2A	26268	79027;79028;79029	chr2:178559626;178559625;178559624	chr2:179424353;179424352;179424351
N2B	19771	59536;59537;59538	chr2:178559626;178559625;178559624	chr2:179424353;179424352;179424351
Novex-1	19896	59911;59912;59913	chr2:178559626;178559625;178559624	chr2:179424353;179424352;179424351
Novex-2	19963	60112;60113;60114	chr2:178559626;178559625;178559624	chr2:179424353;179424352;179424351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-144
• Domain position: 82
• Structural Position: 169
• Q(SASA): 0.1546
• 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
L/V	rs1335461948	None	0.004	N	0.331	0.053	0.381916209588	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
L/V	rs1335461948	None	0.004	N	0.331	0.053	0.381916209588	gnomAD-4.0.0	6.5703E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46968E-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
L/A	0.4262	ambiguous	0.3678	ambiguous	-1.344	Destabilizing	0.157	N	0.621	neutral	None	None	None	None	N
L/C	0.5708	likely_pathogenic	0.5503	ambiguous	-1.318	Destabilizing	0.968	D	0.721	prob.delet.	None	None	None	None	N
L/D	0.9425	likely_pathogenic	0.9208	pathogenic	0.105	Stabilizing	0.726	D	0.803	deleterious	None	None	None	None	N
L/E	0.7492	likely_pathogenic	0.6903	pathogenic	0.158	Stabilizing	0.726	D	0.783	deleterious	None	None	None	None	N
L/F	0.1823	likely_benign	0.1663	benign	-0.775	Destabilizing	0.567	D	0.655	neutral	None	None	None	None	N
L/G	0.8191	likely_pathogenic	0.7769	pathogenic	-1.673	Destabilizing	0.567	D	0.769	deleterious	None	None	None	None	N
L/H	0.5095	ambiguous	0.4605	ambiguous	-0.761	Destabilizing	0.968	D	0.781	deleterious	None	None	None	None	N
L/I	0.1267	likely_benign	0.1109	benign	-0.51	Destabilizing	0.001	N	0.415	neutral	None	None	None	None	N
L/K	0.593	likely_pathogenic	0.5511	ambiguous	-0.747	Destabilizing	0.567	D	0.753	deleterious	None	None	None	None	N
L/M	0.1135	likely_benign	0.1016	benign	-0.752	Destabilizing	0.02	N	0.541	neutral	D	0.522591834	None	None	N
L/N	0.7905	likely_pathogenic	0.7469	pathogenic	-0.744	Destabilizing	0.726	D	0.804	deleterious	None	None	None	None	N
L/P	0.9778	likely_pathogenic	0.9721	pathogenic	-0.757	Destabilizing	0.859	D	0.805	deleterious	N	0.492213696	None	None	N
L/Q	0.3632	ambiguous	0.3205	benign	-0.733	Destabilizing	0.497	N	0.782	deleterious	N	0.514086994	None	None	N
L/R	0.5065	ambiguous	0.4737	ambiguous	-0.403	Destabilizing	0.497	N	0.777	deleterious	N	0.495501234	None	None	N
L/S	0.6144	likely_pathogenic	0.5446	ambiguous	-1.521	Destabilizing	0.567	D	0.723	prob.delet.	None	None	None	None	N
L/T	0.4686	ambiguous	0.4038	ambiguous	-1.319	Destabilizing	0.272	N	0.685	prob.neutral	None	None	None	None	N
L/V	0.1185	likely_benign	0.1038	benign	-0.757	Destabilizing	0.004	N	0.331	neutral	N	0.42198491	None	None	N
L/W	0.5379	ambiguous	0.5067	ambiguous	-0.767	Destabilizing	0.968	D	0.759	deleterious	None	None	None	None	N
L/Y	0.4955	ambiguous	0.4602	ambiguous	-0.556	Destabilizing	0.726	D	0.738	prob.delet.	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.