TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29919	89980;89981;89982	chr2:178553145;178553144;178553143	chr2:179417872;179417871;179417870
N2AB	28278	85057;85058;85059	chr2:178553145;178553144;178553143	chr2:179417872;179417871;179417870
N2A	27351	82276;82277;82278	chr2:178553145;178553144;178553143	chr2:179417872;179417871;179417870
N2B	20854	62785;62786;62787	chr2:178553145;178553144;178553143	chr2:179417872;179417871;179417870
Novex-1	20979	63160;63161;63162	chr2:178553145;178553144;178553143	chr2:179417872;179417871;179417870
Novex-2	21046	63361;63362;63363	chr2:178553145;178553144;178553143	chr2:179417872;179417871;179417870
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-147
• Domain position: 78
• Structural Position: 164
• Q(SASA): 0.2521
• 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
G/D	rs759930753	None	1.0	D	0.872	0.764	0.562917172789	gnomAD-4.0.0	4.10828E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.4008E-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
G/A	0.4382	ambiguous	0.4627	ambiguous	-0.277	Destabilizing	1.0	D	0.747	deleterious	D	0.594800052	None	None	I
G/C	0.6941	likely_pathogenic	0.6921	pathogenic	-0.87	Destabilizing	1.0	D	0.829	deleterious	D	0.639425667	None	None	I
G/D	0.7509	likely_pathogenic	0.726	pathogenic	-0.775	Destabilizing	1.0	D	0.872	deleterious	D	0.605772511	None	None	I
G/E	0.7937	likely_pathogenic	0.7858	pathogenic	-0.944	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/F	0.9545	likely_pathogenic	0.9515	pathogenic	-1.086	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
G/H	0.9195	likely_pathogenic	0.9113	pathogenic	-0.482	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/I	0.9072	likely_pathogenic	0.9042	pathogenic	-0.51	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/K	0.9066	likely_pathogenic	0.8987	pathogenic	-0.827	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
G/L	0.8719	likely_pathogenic	0.869	pathogenic	-0.51	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
G/M	0.9201	likely_pathogenic	0.918	pathogenic	-0.602	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/N	0.8108	likely_pathogenic	0.7986	pathogenic	-0.434	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/P	0.9866	likely_pathogenic	0.9839	pathogenic	-0.404	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
G/Q	0.8473	likely_pathogenic	0.8436	pathogenic	-0.736	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
G/R	0.8216	likely_pathogenic	0.8085	pathogenic	-0.362	Destabilizing	1.0	D	0.889	deleterious	D	0.62913006	None	None	I
G/S	0.3036	likely_benign	0.3063	benign	-0.521	Destabilizing	1.0	D	0.813	deleterious	D	0.592569486	None	None	I
G/T	0.6509	likely_pathogenic	0.6567	pathogenic	-0.633	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
G/V	0.8161	likely_pathogenic	0.8145	pathogenic	-0.404	Destabilizing	1.0	D	0.855	deleterious	D	0.623002697	None	None	I
G/W	0.9053	likely_pathogenic	0.887	pathogenic	-1.212	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
G/Y	0.9302	likely_pathogenic	0.9214	pathogenic	-0.89	Destabilizing	1.0	D	0.86	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.