TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5272	16039;16040;16041	chr2:178733479;178733478;178733477	chr2:179598206;179598205;179598204
N2AB	4955	15088;15089;15090	chr2:178733479;178733478;178733477	chr2:179598206;179598205;179598204
N2A	4028	12307;12308;12309	chr2:178733479;178733478;178733477	chr2:179598206;179598205;179598204
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-36
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.688
• 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
V/M	rs746406893	-0.216	0.999	D	0.495	0.658	0.830710548829	gnomAD-2.1.1	2.86E-05	None	None	None	None	I	None	2.48077E-04	2.83E-05	None	0	0	None	0	None	0	7.84E-06	0
V/M	rs746406893	-0.216	0.999	D	0.495	0.658	0.830710548829	gnomAD-3.1.2	7.88E-05	None	None	None	None	I	None	1.92985E-04	1.30907E-04	0	0	0	None	0	0	1.47E-05	0	4.78469E-04
V/M	rs746406893	-0.216	0.999	D	0.495	0.658	0.830710548829	gnomAD-4.0.0	1.92121E-05	None	None	None	None	I	None	2.93662E-04	5.0005E-05	None	0	0	None	0	0	4.23834E-06	0	1.60128E-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
V/A	0.5988	likely_pathogenic	0.5064	ambiguous	-1.591	Destabilizing	0.989	D	0.445	neutral	D	0.603219916	None	None	I
V/C	0.9476	likely_pathogenic	0.9272	pathogenic	-1.114	Destabilizing	1.0	D	0.439	neutral	None	None	None	None	I
V/D	0.9678	likely_pathogenic	0.9468	pathogenic	-1.251	Destabilizing	0.999	D	0.536	neutral	None	None	None	None	I
V/E	0.9259	likely_pathogenic	0.8772	pathogenic	-1.2	Destabilizing	0.998	D	0.455	neutral	D	0.722636044	None	None	I
V/F	0.7242	likely_pathogenic	0.6018	pathogenic	-1.142	Destabilizing	1.0	D	0.451	neutral	None	None	None	None	I
V/G	0.6849	likely_pathogenic	0.6262	pathogenic	-1.967	Destabilizing	0.998	D	0.515	neutral	D	0.770772647	None	None	I
V/H	0.9814	likely_pathogenic	0.9637	pathogenic	-1.499	Destabilizing	1.0	D	0.527	neutral	None	None	None	None	I
V/I	0.1412	likely_benign	0.1295	benign	-0.634	Destabilizing	0.997	D	0.491	neutral	None	None	None	None	I
V/K	0.9494	likely_pathogenic	0.8889	pathogenic	-1.139	Destabilizing	0.999	D	0.455	neutral	None	None	None	None	I
V/L	0.712	likely_pathogenic	0.6013	pathogenic	-0.634	Destabilizing	0.987	D	0.47	neutral	D	0.607992112	None	None	I
V/M	0.5455	ambiguous	0.4661	ambiguous	-0.557	Destabilizing	0.999	D	0.495	neutral	D	0.804446607	None	None	I
V/N	0.9301	likely_pathogenic	0.8866	pathogenic	-1.015	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	I
V/P	0.991	likely_pathogenic	0.9846	pathogenic	-0.919	Destabilizing	0.269	N	0.315	neutral	None	None	None	None	I
V/Q	0.9281	likely_pathogenic	0.8822	pathogenic	-1.115	Destabilizing	1.0	D	0.475	neutral	None	None	None	None	I
V/R	0.9361	likely_pathogenic	0.8732	pathogenic	-0.745	Destabilizing	1.0	D	0.545	neutral	None	None	None	None	I
V/S	0.8404	likely_pathogenic	0.7773	pathogenic	-1.648	Destabilizing	0.999	D	0.436	neutral	None	None	None	None	I
V/T	0.6555	likely_pathogenic	0.6037	pathogenic	-1.474	Destabilizing	0.996	D	0.491	neutral	None	None	None	None	I
V/W	0.9924	likely_pathogenic	0.9861	pathogenic	-1.37	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	I
V/Y	0.9592	likely_pathogenic	0.9287	pathogenic	-1.042	Destabilizing	1.0	D	0.449	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.