TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28831	86716;86717;86718	chr2:178559641;178559640;178559639	chr2:179424368;179424367;179424366
N2AB	27190	81793;81794;81795	chr2:178559641;178559640;178559639	chr2:179424368;179424367;179424366
N2A	26263	79012;79013;79014	chr2:178559641;178559640;178559639	chr2:179424368;179424367;179424366
N2B	19766	59521;59522;59523	chr2:178559641;178559640;178559639	chr2:179424368;179424367;179424366
Novex-1	19891	59896;59897;59898	chr2:178559641;178559640;178559639	chr2:179424368;179424367;179424366
Novex-2	19958	60097;60098;60099	chr2:178559641;178559640;178559639	chr2:179424368;179424367;179424366
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-144
• Domain position: 77
• Structural Position: 163
• Q(SASA): 0.7997
• Predicted PPI site: I

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	rs755136760	-0.696	0.884	N	0.452	0.188	0.554957464841	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	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	0.1826	likely_benign	0.172	benign	-0.452	Destabilizing	0.016	N	0.338	neutral	None	None	None	None	I
L/C	0.3613	ambiguous	0.3388	benign	-0.844	Destabilizing	0.996	D	0.564	neutral	None	None	None	None	I
L/D	0.5993	likely_pathogenic	0.5461	ambiguous	-0.145	Destabilizing	0.91	D	0.559	neutral	None	None	None	None	I
L/E	0.3712	ambiguous	0.3288	benign	-0.236	Destabilizing	0.742	D	0.531	neutral	None	None	None	None	I
L/F	0.1208	likely_benign	0.1023	benign	-0.646	Destabilizing	0.884	D	0.452	neutral	N	0.456329557	None	None	I
L/G	0.4082	ambiguous	0.3754	ambiguous	-0.536	Destabilizing	0.59	D	0.519	neutral	None	None	None	None	I
L/H	0.187	likely_benign	0.1661	benign	0.037	Stabilizing	0.996	D	0.568	neutral	None	None	None	None	I
L/I	0.0817	likely_benign	0.0798	benign	-0.349	Destabilizing	0.009	N	0.305	neutral	None	None	None	None	I
L/K	0.2371	likely_benign	0.2114	benign	-0.327	Destabilizing	0.742	D	0.533	neutral	None	None	None	None	I
L/M	0.1169	likely_benign	0.1111	benign	-0.608	Destabilizing	0.884	D	0.451	neutral	N	0.488788692	None	None	I
L/N	0.2684	likely_benign	0.2499	benign	-0.202	Destabilizing	0.91	D	0.564	neutral	None	None	None	None	I
L/P	0.5919	likely_pathogenic	0.5347	ambiguous	-0.357	Destabilizing	0.953	D	0.566	neutral	None	None	None	None	I
L/Q	0.1362	likely_benign	0.1253	benign	-0.358	Destabilizing	0.91	D	0.585	neutral	None	None	None	None	I
L/R	0.166	likely_benign	0.1467	benign	0.091	Stabilizing	0.91	D	0.585	neutral	None	None	None	None	I
L/S	0.1897	likely_benign	0.1768	benign	-0.596	Destabilizing	0.028	N	0.505	neutral	N	0.419600753	None	None	I
L/T	0.1793	likely_benign	0.1715	benign	-0.588	Destabilizing	0.59	D	0.453	neutral	None	None	None	None	I
L/V	0.0809	likely_benign	0.0779	benign	-0.357	Destabilizing	0.003	N	0.268	neutral	N	0.433124623	None	None	I
L/W	0.2917	likely_benign	0.2462	benign	-0.664	Destabilizing	0.994	D	0.605	neutral	N	0.51426314	None	None	I
L/Y	0.3121	likely_benign	0.257	benign	-0.436	Destabilizing	0.953	D	0.547	neutral	None	None	None	None	I

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.