TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33573	100942;100943;100944	chr2:178536030;178536029;178536028	chr2:179400757;179400756;179400755
N2AB	31932	96019;96020;96021	chr2:178536030;178536029;178536028	chr2:179400757;179400756;179400755
N2A	31005	93238;93239;93240	chr2:178536030;178536029;178536028	chr2:179400757;179400756;179400755
N2B	24508	73747;73748;73749	chr2:178536030;178536029;178536028	chr2:179400757;179400756;179400755
Novex-1	24633	74122;74123;74124	chr2:178536030;178536029;178536028	chr2:179400757;179400756;179400755
Novex-2	24700	74323;74324;74325	chr2:178536030;178536029;178536028	chr2:179400757;179400756;179400755
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-158
• Domain position: 78
• Structural Position: 159
• Q(SASA): 0.2324
• 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
T/I	rs2154137156	None	1.0	D	0.765	0.527	0.70075097299	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.92827E-04	None	0	0	0	0	0
T/I	rs2154137156	None	1.0	D	0.765	0.527	0.70075097299	gnomAD-4.0.0	1.90449E-06	None	None	None	None	N	None	0	0	None	0	2.24669E-05	None	0	0	0	2.38578E-05	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
T/A	0.2355	likely_benign	0.2313	benign	-0.903	Destabilizing	0.979	D	0.607	neutral	N	0.517052729	None	None	N
T/C	0.8019	likely_pathogenic	0.8134	pathogenic	-0.631	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
T/D	0.9212	likely_pathogenic	0.8897	pathogenic	-0.66	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
T/E	0.8391	likely_pathogenic	0.7955	pathogenic	-0.633	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/F	0.7106	likely_pathogenic	0.7169	pathogenic	-0.933	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/G	0.6549	likely_pathogenic	0.6437	pathogenic	-1.187	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
T/H	0.7702	likely_pathogenic	0.7509	pathogenic	-1.485	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
T/I	0.472	ambiguous	0.503	ambiguous	-0.228	Destabilizing	1.0	D	0.765	deleterious	D	0.527328437	None	None	N
T/K	0.7561	likely_pathogenic	0.7467	pathogenic	-0.802	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/L	0.3685	ambiguous	0.3915	ambiguous	-0.228	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
T/M	0.2491	likely_benign	0.2742	benign	0.124	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/N	0.4773	ambiguous	0.4655	ambiguous	-0.882	Destabilizing	0.998	D	0.775	deleterious	D	0.536331923	None	None	N
T/P	0.9202	likely_pathogenic	0.9234	pathogenic	-0.42	Destabilizing	0.998	D	0.753	deleterious	D	0.529034999	None	None	N
T/Q	0.6467	likely_pathogenic	0.619	pathogenic	-1.047	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
T/R	0.6955	likely_pathogenic	0.6927	pathogenic	-0.583	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/S	0.2696	likely_benign	0.2408	benign	-1.14	Destabilizing	0.979	D	0.611	neutral	N	0.473435237	None	None	N
T/V	0.2858	likely_benign	0.3304	benign	-0.42	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
T/W	0.9477	likely_pathogenic	0.947	pathogenic	-0.879	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
T/Y	0.8078	likely_pathogenic	0.8052	pathogenic	-0.627	Destabilizing	1.0	D	0.777	deleterious	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.