TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1120	3583;3584;3585	chr2:178782234;178782233;178782232	chr2:179646961;179646960;179646959
N2AB	1120	3583;3584;3585	chr2:178782234;178782233;178782232	chr2:179646961;179646960;179646959
N2A	1120	3583;3584;3585	chr2:178782234;178782233;178782232	chr2:179646961;179646960;179646959
N2B	1074	3445;3446;3447	chr2:178782234;178782233;178782232	chr2:179646961;179646960;179646959
Novex-1	1074	3445;3446;3447	chr2:178782234;178782233;178782232	chr2:179646961;179646960;179646959
Novex-2	1074	3445;3446;3447	chr2:178782234;178782233;178782232	chr2:179646961;179646960;179646959
Novex-3	1120	3583;3584;3585	chr2:178782234;178782233;178782232	chr2:179646961;179646960;179646959

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-4
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.3718
• 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/F	None	None	0.003	N	0.233	0.171	0.651281849334	gnomAD-4.0.0	1.59053E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8566E-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
V/A	0.6225	likely_pathogenic	0.5087	ambiguous	-0.491	Destabilizing	0.165	N	0.272	neutral	N	0.451134931	None	None	N
V/C	0.951	likely_pathogenic	0.9243	pathogenic	-0.781	Destabilizing	0.981	D	0.361	neutral	None	None	None	None	N
V/D	0.884	likely_pathogenic	0.7969	pathogenic	-0.172	Destabilizing	0.912	D	0.449	neutral	N	0.483362575	None	None	N
V/E	0.7251	likely_pathogenic	0.6056	pathogenic	-0.264	Destabilizing	0.932	D	0.427	neutral	None	None	None	None	N
V/F	0.3147	likely_benign	0.2575	benign	-0.604	Destabilizing	0.003	N	0.233	neutral	N	0.50734685	None	None	N
V/G	0.7059	likely_pathogenic	0.5939	pathogenic	-0.629	Destabilizing	0.773	D	0.421	neutral	N	0.419468945	None	None	N
V/H	0.8854	likely_pathogenic	0.8097	pathogenic	-0.084	Destabilizing	0.981	D	0.45	neutral	None	None	None	None	N
V/I	0.0764	likely_benign	0.0737	benign	-0.268	Destabilizing	0.001	N	0.205	neutral	N	0.460580718	None	None	N
V/K	0.7698	likely_pathogenic	0.6386	pathogenic	-0.496	Destabilizing	0.818	D	0.422	neutral	None	None	None	None	N
V/L	0.3877	ambiguous	0.3365	benign	-0.268	Destabilizing	0.001	N	0.146	neutral	N	0.481305799	None	None	N
V/M	0.2612	likely_benign	0.2225	benign	-0.47	Destabilizing	0.69	D	0.36	neutral	None	None	None	None	N
V/N	0.6843	likely_pathogenic	0.5617	ambiguous	-0.338	Destabilizing	0.932	D	0.437	neutral	None	None	None	None	N
V/P	0.986	likely_pathogenic	0.9812	pathogenic	-0.309	Destabilizing	0.932	D	0.423	neutral	None	None	None	None	N
V/Q	0.6639	likely_pathogenic	0.5508	ambiguous	-0.523	Destabilizing	0.932	D	0.417	neutral	None	None	None	None	N
V/R	0.7271	likely_pathogenic	0.6108	pathogenic	-0.002	Destabilizing	0.818	D	0.443	neutral	None	None	None	None	N
V/S	0.6355	likely_pathogenic	0.5124	ambiguous	-0.73	Destabilizing	0.818	D	0.402	neutral	None	None	None	None	N
V/T	0.5563	ambiguous	0.445	ambiguous	-0.716	Destabilizing	0.388	N	0.241	neutral	None	None	None	None	N
V/W	0.9658	likely_pathogenic	0.9482	pathogenic	-0.686	Destabilizing	0.981	D	0.473	neutral	None	None	None	None	N
V/Y	0.8042	likely_pathogenic	0.73	pathogenic	-0.403	Destabilizing	0.527	D	0.336	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.