TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14358	43297;43298;43299	chr2:178633201;178633200;178633199	chr2:179497928;179497927;179497926
N2AB	12717	38374;38375;38376	chr2:178633201;178633200;178633199	chr2:179497928;179497927;179497926
N2A	11790	35593;35594;35595	chr2:178633201;178633200;178633199	chr2:179497928;179497927;179497926
N2B	5293	16102;16103;16104	chr2:178633201;178633200;178633199	chr2:179497928;179497927;179497926
Novex-1	5418	16477;16478;16479	chr2:178633201;178633200;178633199	chr2:179497928;179497927;179497926
Novex-2	5485	16678;16679;16680	chr2:178633201;178633200;178633199	chr2:179497928;179497927;179497926
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-94
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.2192
• 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/F	rs1200127540	-1.388	0.999	D	0.779	0.304	0.351830644314	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
L/F	rs1200127540	-1.388	0.999	D	0.779	0.304	0.351830644314	gnomAD-4.0.0	1.59387E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02939E-05

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	0.8534	likely_pathogenic	0.8378	pathogenic	-2.254	Highly Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
L/C	0.8833	likely_pathogenic	0.8801	pathogenic	-1.458	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/D	0.9952	likely_pathogenic	0.9951	pathogenic	-1.975	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/E	0.953	likely_pathogenic	0.9522	pathogenic	-1.825	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
L/F	0.4179	ambiguous	0.3779	ambiguous	-1.39	Destabilizing	0.999	D	0.779	deleterious	D	0.609781837	None	None	N
L/G	0.9776	likely_pathogenic	0.9765	pathogenic	-2.71	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
L/H	0.9043	likely_pathogenic	0.8997	pathogenic	-1.834	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/I	0.1296	likely_benign	0.1186	benign	-0.98	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
L/K	0.8978	likely_pathogenic	0.8964	pathogenic	-1.704	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
L/M	0.2916	likely_benign	0.2606	benign	-0.842	Destabilizing	0.999	D	0.739	deleterious	D	0.610815203	None	None	N
L/N	0.9708	likely_pathogenic	0.976	pathogenic	-1.814	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
L/P	0.9704	likely_pathogenic	0.9704	pathogenic	-1.381	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/Q	0.8498	likely_pathogenic	0.8412	pathogenic	-1.79	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/R	0.8581	likely_pathogenic	0.8565	pathogenic	-1.279	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/S	0.9542	likely_pathogenic	0.9513	pathogenic	-2.503	Highly Destabilizing	0.999	D	0.854	deleterious	D	0.650325893	None	None	N
L/T	0.8748	likely_pathogenic	0.862	pathogenic	-2.207	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
L/V	0.171	likely_benign	0.1558	benign	-1.381	Destabilizing	0.997	D	0.648	neutral	N	0.495477938	None	None	N
L/W	0.8271	likely_pathogenic	0.8071	pathogenic	-1.571	Destabilizing	1.0	D	0.806	deleterious	D	0.652981016	None	None	N
L/Y	0.8483	likely_pathogenic	0.8381	pathogenic	-1.327	Destabilizing	0.999	D	0.867	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.