TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22506	67741;67742;67743	chr2:178579681;178579680;178579679	chr2:179444408;179444407;179444406
N2AB	20865	62818;62819;62820	chr2:178579681;178579680;178579679	chr2:179444408;179444407;179444406
N2A	19938	60037;60038;60039	chr2:178579681;178579680;178579679	chr2:179444408;179444407;179444406
N2B	13441	40546;40547;40548	chr2:178579681;178579680;178579679	chr2:179444408;179444407;179444406
Novex-1	13566	40921;40922;40923	chr2:178579681;178579680;178579679	chr2:179444408;179444407;179444406
Novex-2	13633	41122;41123;41124	chr2:178579681;178579680;178579679	chr2:179444408;179444407;179444406
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-51
• Domain position: 56
• Structural Position: 89
• Q(SASA): 0.1889
• 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
L/P	None	None	0.773	N	0.591	0.338	0.561523483268	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86015E-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
L/A	0.305	likely_benign	0.2665	benign	-1.853	Destabilizing	0.008	N	0.284	neutral	None	None	None	None	N
L/C	0.4309	ambiguous	0.4018	ambiguous	-1.083	Destabilizing	0.981	D	0.512	neutral	None	None	None	None	N
L/D	0.7416	likely_pathogenic	0.7145	pathogenic	-1.591	Destabilizing	0.69	D	0.592	neutral	None	None	None	None	N
L/E	0.4087	ambiguous	0.3526	ambiguous	-1.45	Destabilizing	0.388	N	0.553	neutral	None	None	None	None	N
L/F	0.1862	likely_benign	0.2083	benign	-1.093	Destabilizing	0.69	D	0.482	neutral	None	None	None	None	N
L/G	0.4363	ambiguous	0.4032	ambiguous	-2.292	Highly Destabilizing	0.388	N	0.528	neutral	None	None	None	None	N
L/H	0.2841	likely_benign	0.2795	benign	-1.452	Destabilizing	0.981	D	0.584	neutral	None	None	None	None	N
L/I	0.1632	likely_benign	0.1761	benign	-0.647	Destabilizing	0.193	N	0.417	neutral	N	0.484483658	None	None	N
L/K	0.2989	likely_benign	0.2612	benign	-1.264	Destabilizing	0.388	N	0.534	neutral	None	None	None	None	N
L/M	0.11	likely_benign	0.1061	benign	-0.567	Destabilizing	0.008	N	0.309	neutral	None	None	None	None	N
L/N	0.3431	ambiguous	0.2943	benign	-1.421	Destabilizing	0.69	D	0.592	neutral	None	None	None	None	N
L/P	0.1948	likely_benign	0.1691	benign	-1.024	Destabilizing	0.773	D	0.591	neutral	N	0.443655756	None	None	N
L/Q	0.1494	likely_benign	0.1241	benign	-1.407	Destabilizing	0.773	D	0.574	neutral	N	0.476709537	None	None	N
L/R	0.2268	likely_benign	0.2251	benign	-0.862	Destabilizing	0.627	D	0.592	neutral	N	0.4099859	None	None	N
L/S	0.2739	likely_benign	0.2568	benign	-2.086	Highly Destabilizing	0.024	N	0.482	neutral	None	None	None	None	N
L/T	0.1739	likely_benign	0.1499	benign	-1.806	Destabilizing	0.004	N	0.281	neutral	None	None	None	None	N
L/V	0.1268	likely_benign	0.129	benign	-1.024	Destabilizing	0.09	N	0.429	neutral	N	0.483963583	None	None	N
L/W	0.3353	likely_benign	0.411	ambiguous	-1.314	Destabilizing	0.981	D	0.594	neutral	None	None	None	None	N
L/Y	0.4072	ambiguous	0.4291	ambiguous	-1.003	Destabilizing	0.818	D	0.529	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.