TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21805	65638;65639;65640	chr2:178583769;178583768;178583767	chr2:179448496;179448495;179448494
N2AB	20164	60715;60716;60717	chr2:178583769;178583768;178583767	chr2:179448496;179448495;179448494
N2A	19237	57934;57935;57936	chr2:178583769;178583768;178583767	chr2:179448496;179448495;179448494
N2B	12740	38443;38444;38445	chr2:178583769;178583768;178583767	chr2:179448496;179448495;179448494
Novex-1	12865	38818;38819;38820	chr2:178583769;178583768;178583767	chr2:179448496;179448495;179448494
Novex-2	12932	39019;39020;39021	chr2:178583769;178583768;178583767	chr2:179448496;179448495;179448494
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-46
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4343
• 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
V/E	None	None	None	N	0.351	0.295	0.499535901811	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
V/I	None	None	None	N	0.182	0.119	0.349204839081	gnomAD-4.0.0	1.597E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41663E-04	0	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
V/A	0.2269	likely_benign	0.2064	benign	-0.951	Destabilizing	0.027	N	0.343	neutral	N	0.51511321	None	None	N
V/C	0.6572	likely_pathogenic	0.6363	pathogenic	-0.55	Destabilizing	0.935	D	0.411	neutral	None	None	None	None	N
V/D	0.3403	ambiguous	0.3293	benign	-0.774	Destabilizing	0.081	N	0.399	neutral	None	None	None	None	N
V/E	0.2094	likely_benign	0.214	benign	-0.856	Destabilizing	None	N	0.351	neutral	N	0.494161934	None	None	N
V/F	0.159	likely_benign	0.149	benign	-0.946	Destabilizing	0.38	N	0.464	neutral	None	None	None	None	N
V/G	0.2208	likely_benign	0.2153	benign	-1.16	Destabilizing	0.117	N	0.402	neutral	N	0.4855627	None	None	N
V/H	0.44	ambiguous	0.4258	ambiguous	-0.696	Destabilizing	0.555	D	0.448	neutral	None	None	None	None	N
V/I	0.0763	likely_benign	0.0686	benign	-0.522	Destabilizing	None	N	0.182	neutral	N	0.451621878	None	None	N
V/K	0.2925	likely_benign	0.3033	benign	-0.815	Destabilizing	0.081	N	0.358	neutral	None	None	None	None	N
V/L	0.1546	likely_benign	0.1456	benign	-0.522	Destabilizing	0.009	N	0.353	neutral	N	0.501010549	None	None	N
V/M	0.1334	likely_benign	0.1155	benign	-0.354	Destabilizing	0.38	N	0.465	neutral	None	None	None	None	N
V/N	0.2144	likely_benign	0.1879	benign	-0.474	Destabilizing	0.002	N	0.381	neutral	None	None	None	None	N
V/P	0.8699	likely_pathogenic	0.873	pathogenic	-0.629	Destabilizing	0.555	D	0.449	neutral	None	None	None	None	N
V/Q	0.2116	likely_benign	0.2154	benign	-0.729	Destabilizing	0.235	N	0.449	neutral	None	None	None	None	N
V/R	0.2708	likely_benign	0.2946	benign	-0.217	Destabilizing	0.38	N	0.463	neutral	None	None	None	None	N
V/S	0.2107	likely_benign	0.19	benign	-0.865	Destabilizing	0.081	N	0.374	neutral	None	None	None	None	N
V/T	0.194	likely_benign	0.1625	benign	-0.85	Destabilizing	0.001	N	0.122	neutral	None	None	None	None	N
V/W	0.7199	likely_pathogenic	0.7046	pathogenic	-1.058	Destabilizing	0.935	D	0.499	neutral	None	None	None	None	N
V/Y	0.4478	ambiguous	0.436	ambiguous	-0.785	Destabilizing	0.555	D	0.457	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.