TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31461	94606;94607;94608	chr2:178547144;178547143;178547142	chr2:179411871;179411870;179411869
N2AB	29820	89683;89684;89685	chr2:178547144;178547143;178547142	chr2:179411871;179411870;179411869
N2A	28893	86902;86903;86904	chr2:178547144;178547143;178547142	chr2:179411871;179411870;179411869
N2B	22396	67411;67412;67413	chr2:178547144;178547143;178547142	chr2:179411871;179411870;179411869
Novex-1	22521	67786;67787;67788	chr2:178547144;178547143;178547142	chr2:179411871;179411870;179411869
Novex-2	22588	67987;67988;67989	chr2:178547144;178547143;178547142	chr2:179411871;179411870;179411869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-117
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.3358
• 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
V/L	rs1206905148	None	0.001	N	0.093	0.098	0.213573922156	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs1206905148	None	0.001	N	0.093	0.098	0.213573922156	gnomAD-4.0.0	6.57307E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47037E-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
V/A	0.134	likely_benign	0.1102	benign	-0.616	Destabilizing	0.001	N	0.113	neutral	N	0.437287144	None	None	I
V/C	0.5456	ambiguous	0.4943	ambiguous	-0.593	Destabilizing	0.944	D	0.264	neutral	None	None	None	None	I
V/D	0.3017	likely_benign	0.2705	benign	-0.436	Destabilizing	0.69	D	0.425	neutral	None	None	None	None	I
V/E	0.2586	likely_benign	0.2472	benign	-0.507	Destabilizing	0.627	D	0.396	neutral	N	0.448522858	None	None	I
V/F	0.1197	likely_benign	0.1171	benign	-0.704	Destabilizing	0.69	D	0.335	neutral	None	None	None	None	I
V/G	0.1668	likely_benign	0.1347	benign	-0.776	Destabilizing	0.193	N	0.406	neutral	N	0.456315622	None	None	I
V/H	0.4156	ambiguous	0.3731	ambiguous	-0.184	Destabilizing	0.981	D	0.365	neutral	None	None	None	None	I
V/I	0.0628	likely_benign	0.0661	benign	-0.32	Destabilizing	0.004	N	0.139	neutral	None	None	None	None	I
V/K	0.3517	ambiguous	0.3474	ambiguous	-0.494	Destabilizing	0.69	D	0.4	neutral	None	None	None	None	I
V/L	0.1116	likely_benign	0.1023	benign	-0.32	Destabilizing	0.001	N	0.093	neutral	N	0.438423295	None	None	I
V/M	0.0866	likely_benign	0.085	benign	-0.497	Destabilizing	0.627	D	0.345	neutral	N	0.470458355	None	None	I
V/N	0.1466	likely_benign	0.122	benign	-0.294	Destabilizing	0.69	D	0.41	neutral	None	None	None	None	I
V/P	0.7317	likely_pathogenic	0.67	pathogenic	-0.386	Destabilizing	0.818	D	0.386	neutral	None	None	None	None	I
V/Q	0.2616	likely_benign	0.2322	benign	-0.483	Destabilizing	0.818	D	0.352	neutral	None	None	None	None	I
V/R	0.3483	ambiguous	0.3482	ambiguous	0.008	Stabilizing	0.69	D	0.411	neutral	None	None	None	None	I
V/S	0.1193	likely_benign	0.0981	benign	-0.654	Destabilizing	0.241	N	0.313	neutral	None	None	None	None	I
V/T	0.1219	likely_benign	0.1088	benign	-0.622	Destabilizing	0.008	N	0.175	neutral	None	None	None	None	I
V/W	0.6549	likely_pathogenic	0.6302	pathogenic	-0.799	Destabilizing	0.981	D	0.401	neutral	None	None	None	None	I
V/Y	0.3321	likely_benign	0.3022	benign	-0.508	Destabilizing	0.932	D	0.307	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.