TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24642	74149;74150;74151	chr2:178572208;178572207;178572206	chr2:179436935;179436934;179436933
N2AB	23001	69226;69227;69228	chr2:178572208;178572207;178572206	chr2:179436935;179436934;179436933
N2A	22074	66445;66446;66447	chr2:178572208;178572207;178572206	chr2:179436935;179436934;179436933
N2B	15577	46954;46955;46956	chr2:178572208;178572207;178572206	chr2:179436935;179436934;179436933
Novex-1	15702	47329;47330;47331	chr2:178572208;178572207;178572206	chr2:179436935;179436934;179436933
Novex-2	15769	47530;47531;47532	chr2:178572208;178572207;178572206	chr2:179436935;179436934;179436933
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-67
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.1986
• 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
H/R	None	None	0.951	N	0.446	0.242	0.269111216191	gnomAD-4.0.0	4.77602E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71863E-06	1.43295E-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
H/A	0.7675	likely_pathogenic	0.7141	pathogenic	0.303	Stabilizing	0.901	D	0.581	neutral	None	None	None	None	N
H/C	0.5069	ambiguous	0.4896	ambiguous	0.599	Stabilizing	0.996	D	0.683	prob.neutral	None	None	None	None	N
H/D	0.7243	likely_pathogenic	0.6315	pathogenic	0.113	Stabilizing	0.978	D	0.487	neutral	N	0.43420398	None	None	N
H/E	0.8431	likely_pathogenic	0.7697	pathogenic	0.125	Stabilizing	0.885	D	0.497	neutral	None	None	None	None	N
H/F	0.4808	ambiguous	0.3985	ambiguous	0.828	Stabilizing	0.718	D	0.535	neutral	None	None	None	None	N
H/G	0.7457	likely_pathogenic	0.7074	pathogenic	0.051	Stabilizing	0.949	D	0.55	neutral	None	None	None	None	N
H/I	0.8084	likely_pathogenic	0.7141	pathogenic	0.931	Stabilizing	0.927	D	0.657	neutral	None	None	None	None	N
H/K	0.8133	likely_pathogenic	0.7597	pathogenic	0.279	Stabilizing	0.963	D	0.481	neutral	None	None	None	None	N
H/L	0.5429	ambiguous	0.4351	ambiguous	0.931	Stabilizing	0.579	D	0.592	neutral	N	0.500178256	None	None	N
H/M	0.7821	likely_pathogenic	0.7167	pathogenic	0.706	Stabilizing	0.997	D	0.629	neutral	None	None	None	None	N
H/N	0.2688	likely_benign	0.2279	benign	0.28	Stabilizing	0.808	D	0.525	neutral	N	0.45223238	None	None	N
H/P	0.9542	likely_pathogenic	0.9347	pathogenic	0.747	Stabilizing	0.978	D	0.631	neutral	N	0.493406999	None	None	N
H/Q	0.6617	likely_pathogenic	0.582	pathogenic	0.347	Stabilizing	0.953	D	0.471	neutral	N	0.500351614	None	None	N
H/R	0.5986	likely_pathogenic	0.5138	ambiguous	-0.189	Destabilizing	0.951	D	0.446	neutral	N	0.474666523	None	None	N
H/S	0.5275	ambiguous	0.4785	ambiguous	0.298	Stabilizing	0.949	D	0.523	neutral	None	None	None	None	N
H/T	0.6903	likely_pathogenic	0.6115	pathogenic	0.409	Stabilizing	0.951	D	0.537	neutral	None	None	None	None	N
H/V	0.7496	likely_pathogenic	0.6578	pathogenic	0.747	Stabilizing	0.93	D	0.559	neutral	None	None	None	None	N
H/W	0.6631	likely_pathogenic	0.6075	pathogenic	0.786	Stabilizing	0.997	D	0.633	neutral	None	None	None	None	N
H/Y	0.2225	likely_benign	0.1683	benign	1.095	Stabilizing	0.005	N	0.091	neutral	N	0.425720569	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.