TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27693	83302;83303;83304	chr2:178563055;178563054;178563053	chr2:179427782;179427781;179427780
N2AB	26052	78379;78380;78381	chr2:178563055;178563054;178563053	chr2:179427782;179427781;179427780
N2A	25125	75598;75599;75600	chr2:178563055;178563054;178563053	chr2:179427782;179427781;179427780
N2B	18628	56107;56108;56109	chr2:178563055;178563054;178563053	chr2:179427782;179427781;179427780
Novex-1	18753	56482;56483;56484	chr2:178563055;178563054;178563053	chr2:179427782;179427781;179427780
Novex-2	18820	56683;56684;56685	chr2:178563055;178563054;178563053	chr2:179427782;179427781;179427780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-141
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1644
• 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/V	rs1329220257	-0.903	0.618	N	0.589	0.057	0.252162846088	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
L/V	rs1329220257	-0.903	0.618	N	0.589	0.057	0.252162846088	gnomAD-4.0.0	1.59144E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85886E-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	0.8627	likely_pathogenic	0.8395	pathogenic	-2.736	Highly Destabilizing	0.968	D	0.693	prob.neutral	None	None	None	None	I
L/C	0.8824	likely_pathogenic	0.8651	pathogenic	-2.102	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
L/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.289	Highly Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	I
L/E	0.998	likely_pathogenic	0.9968	pathogenic	-3.014	Highly Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	I
L/F	0.8202	likely_pathogenic	0.779	pathogenic	-1.685	Destabilizing	0.988	D	0.775	deleterious	N	0.45453048	None	None	I
L/G	0.9868	likely_pathogenic	0.9811	pathogenic	-3.31	Highly Destabilizing	0.995	D	0.833	deleterious	None	None	None	None	I
L/H	0.995	likely_pathogenic	0.9922	pathogenic	-2.691	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
L/I	0.2866	likely_benign	0.2828	benign	-1.05	Destabilizing	0.142	N	0.341	neutral	N	0.466329467	None	None	I
L/K	0.9964	likely_pathogenic	0.9942	pathogenic	-2.429	Highly Destabilizing	0.995	D	0.822	deleterious	None	None	None	None	I
L/M	0.2699	likely_benign	0.2545	benign	-0.994	Destabilizing	0.991	D	0.76	deleterious	None	None	None	None	I
L/N	0.9974	likely_pathogenic	0.9963	pathogenic	-2.969	Highly Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	I
L/P	0.9972	likely_pathogenic	0.9956	pathogenic	-1.597	Destabilizing	0.998	D	0.85	deleterious	None	None	None	None	I
L/Q	0.986	likely_pathogenic	0.979	pathogenic	-2.749	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
L/R	0.9934	likely_pathogenic	0.9898	pathogenic	-2.188	Highly Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	I
L/S	0.9872	likely_pathogenic	0.9806	pathogenic	-3.626	Highly Destabilizing	0.994	D	0.817	deleterious	N	0.504261342	None	None	I
L/T	0.9562	likely_pathogenic	0.9412	pathogenic	-3.188	Highly Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	I
L/V	0.2706	likely_benign	0.2591	benign	-1.597	Destabilizing	0.618	D	0.589	neutral	N	0.482082779	None	None	I
L/W	0.9913	likely_pathogenic	0.9864	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
L/Y	0.9892	likely_pathogenic	0.9845	pathogenic	-1.777	Destabilizing	0.995	D	0.849	deleterious	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.