TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23587	70984;70985;70986	chr2:178575373;178575372;178575371	chr2:179440100;179440099;179440098
N2AB	21946	66061;66062;66063	chr2:178575373;178575372;178575371	chr2:179440100;179440099;179440098
N2A	21019	63280;63281;63282	chr2:178575373;178575372;178575371	chr2:179440100;179440099;179440098
N2B	14522	43789;43790;43791	chr2:178575373;178575372;178575371	chr2:179440100;179440099;179440098
Novex-1	14647	44164;44165;44166	chr2:178575373;178575372;178575371	chr2:179440100;179440099;179440098
Novex-2	14714	44365;44366;44367	chr2:178575373;178575372;178575371	chr2:179440100;179440099;179440098
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-59
• Domain position: 56
• Structural Position: 88
• Q(SASA): 0.2632
• 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
G/R	None	None	0.055	N	0.365	0.137	0.317084106153	gnomAD-4.0.0	2.7372E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59816E-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
G/A	0.0807	likely_benign	0.0856	benign	-0.333	Destabilizing	None	N	0.105	neutral	N	0.411716696	None	None	N
G/C	0.1834	likely_benign	0.1897	benign	-0.443	Destabilizing	0.676	D	0.381	neutral	None	None	None	None	N
G/D	0.2161	likely_benign	0.209	benign	-0.699	Destabilizing	0.038	N	0.299	neutral	None	None	None	None	N
G/E	0.2213	likely_benign	0.2132	benign	-0.658	Destabilizing	0.055	N	0.299	neutral	N	0.451581806	None	None	N
G/F	0.4458	ambiguous	0.4649	ambiguous	-0.545	Destabilizing	0.356	N	0.399	neutral	None	None	None	None	N
G/H	0.352	ambiguous	0.3562	ambiguous	-0.815	Destabilizing	0.356	N	0.354	neutral	None	None	None	None	N
G/I	0.2064	likely_benign	0.2209	benign	0.233	Stabilizing	0.214	N	0.388	neutral	None	None	None	None	N
G/K	0.4909	ambiguous	0.4855	ambiguous	-0.626	Destabilizing	0.072	N	0.31	neutral	None	None	None	None	N
G/L	0.2567	likely_benign	0.2764	benign	0.233	Stabilizing	0.038	N	0.333	neutral	None	None	None	None	N
G/M	0.2827	likely_benign	0.306	benign	-0.033	Destabilizing	0.356	N	0.382	neutral	None	None	None	None	N
G/N	0.1586	likely_benign	0.1635	benign	-0.567	Destabilizing	None	N	0.11	neutral	None	None	None	None	N
G/P	0.6926	likely_pathogenic	0.731	pathogenic	0.085	Stabilizing	0.214	N	0.371	neutral	None	None	None	None	N
G/Q	0.309	likely_benign	0.3111	benign	-0.579	Destabilizing	0.214	N	0.365	neutral	None	None	None	None	N
G/R	0.4328	ambiguous	0.416	ambiguous	-0.523	Destabilizing	0.055	N	0.365	neutral	N	0.452813957	None	None	N
G/S	0.0748	likely_benign	0.0774	benign	-0.869	Destabilizing	None	N	0.116	neutral	None	None	None	None	N
G/T	0.0874	likely_benign	0.0947	benign	-0.718	Destabilizing	0.001	N	0.253	neutral	None	None	None	None	N
G/V	0.1282	likely_benign	0.1372	benign	0.085	Stabilizing	0.029	N	0.344	neutral	N	0.441076811	None	None	N
G/W	0.4419	ambiguous	0.4267	ambiguous	-1.027	Destabilizing	0.828	D	0.402	neutral	N	0.492195291	None	None	N
G/Y	0.3513	ambiguous	0.3501	ambiguous	-0.46	Destabilizing	0.356	N	0.403	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.