TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32454	97585;97586;97587	chr2:178542396;178542395;178542394	chr2:179407123;179407122;179407121
N2AB	30813	92662;92663;92664	chr2:178542396;178542395;178542394	chr2:179407123;179407122;179407121
N2A	29886	89881;89882;89883	chr2:178542396;178542395;178542394	chr2:179407123;179407122;179407121
N2B	23389	70390;70391;70392	chr2:178542396;178542395;178542394	chr2:179407123;179407122;179407121
Novex-1	23514	70765;70766;70767	chr2:178542396;178542395;178542394	chr2:179407123;179407122;179407121
Novex-2	23581	70966;70967;70968	chr2:178542396;178542395;178542394	chr2:179407123;179407122;179407121
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-124
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1316
• 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
V/A	None	None	0.999	N	0.557	0.294	0.619139198567	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85869E-06	0	0
V/M	None	None	1.0	N	0.696	0.354	0.624195876753	gnomAD-4.0.0	1.59153E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85869E-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
V/A	0.5998	likely_pathogenic	0.5542	ambiguous	-1.204	Destabilizing	0.999	D	0.557	neutral	N	0.477112322	None	None	N
V/C	0.8966	likely_pathogenic	0.8837	pathogenic	-0.892	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/D	0.9784	likely_pathogenic	0.9775	pathogenic	-0.549	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/E	0.9332	likely_pathogenic	0.9371	pathogenic	-0.38	Destabilizing	1.0	D	0.835	deleterious	N	0.486253355	None	None	N
V/F	0.8161	likely_pathogenic	0.8047	pathogenic	-0.619	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/G	0.8331	likely_pathogenic	0.8105	pathogenic	-1.678	Destabilizing	1.0	D	0.857	deleterious	N	0.482339334	None	None	N
V/H	0.9812	likely_pathogenic	0.9812	pathogenic	-1.364	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/I	0.1059	likely_benign	0.1039	benign	0.066	Stabilizing	0.998	D	0.515	neutral	None	None	None	None	N
V/K	0.9616	likely_pathogenic	0.9647	pathogenic	-0.578	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/L	0.6236	likely_pathogenic	0.6026	pathogenic	0.066	Stabilizing	0.997	D	0.544	neutral	N	0.518574802	None	None	N
V/M	0.5094	ambiguous	0.469	ambiguous	-0.185	Destabilizing	1.0	D	0.696	prob.neutral	N	0.509614756	None	None	N
V/N	0.8748	likely_pathogenic	0.8817	pathogenic	-0.705	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/P	0.9552	likely_pathogenic	0.9581	pathogenic	-0.325	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Q	0.9045	likely_pathogenic	0.9128	pathogenic	-0.555	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/R	0.9503	likely_pathogenic	0.9498	pathogenic	-0.619	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/S	0.7584	likely_pathogenic	0.7334	pathogenic	-1.462	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/T	0.6212	likely_pathogenic	0.5987	pathogenic	-1.137	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
V/W	0.9965	likely_pathogenic	0.9958	pathogenic	-0.952	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/Y	0.9807	likely_pathogenic	0.979	pathogenic	-0.514	Destabilizing	1.0	D	0.839	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.