TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21634	65125;65126;65127	chr2:178584741;178584740;178584739	chr2:179449468;179449467;179449466
N2AB	19993	60202;60203;60204	chr2:178584741;178584740;178584739	chr2:179449468;179449467;179449466
N2A	19066	57421;57422;57423	chr2:178584741;178584740;178584739	chr2:179449468;179449467;179449466
N2B	12569	37930;37931;37932	chr2:178584741;178584740;178584739	chr2:179449468;179449467;179449466
Novex-1	12694	38305;38306;38307	chr2:178584741;178584740;178584739	chr2:179449468;179449467;179449466
Novex-2	12761	38506;38507;38508	chr2:178584741;178584740;178584739	chr2:179449468;179449467;179449466
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-44
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0959
• 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/I	rs1191272248	None	0.997	N	0.557	0.318	0.637113853397	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93874E-04	None	0	0	0	0	0
V/I	rs1191272248	None	0.997	N	0.557	0.318	0.637113853397	gnomAD-4.0.0	2.56327E-06	None	None	None	None	N	None	0	0	None	0	2.42648E-05	None	0	0	2.39418E-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	0.8816	likely_pathogenic	0.8865	pathogenic	-2.723	Highly Destabilizing	0.999	D	0.637	neutral	D	0.556758629	None	None	N
V/C	0.9614	likely_pathogenic	0.9619	pathogenic	-1.854	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/D	0.9987	likely_pathogenic	0.9991	pathogenic	-3.27	Highly Destabilizing	1.0	D	0.825	deleterious	D	0.63969891	None	None	N
V/E	0.9953	likely_pathogenic	0.9965	pathogenic	-2.974	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/F	0.9614	likely_pathogenic	0.9573	pathogenic	-1.509	Destabilizing	1.0	D	0.739	prob.delet.	D	0.574862884	None	None	N
V/G	0.923	likely_pathogenic	0.932	pathogenic	-3.245	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.63969891	None	None	N
V/H	0.9991	likely_pathogenic	0.9993	pathogenic	-2.894	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
V/I	0.1263	likely_benign	0.1203	benign	-1.161	Destabilizing	0.997	D	0.557	neutral	N	0.480326711	None	None	N
V/K	0.9965	likely_pathogenic	0.9975	pathogenic	-2.136	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/L	0.8034	likely_pathogenic	0.789	pathogenic	-1.161	Destabilizing	0.997	D	0.661	neutral	N	0.517152623	None	None	N
V/M	0.86	likely_pathogenic	0.8635	pathogenic	-1.456	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
V/N	0.9951	likely_pathogenic	0.9963	pathogenic	-2.811	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
V/P	0.9954	likely_pathogenic	0.9968	pathogenic	-1.673	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/Q	0.9943	likely_pathogenic	0.9958	pathogenic	-2.454	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/R	0.993	likely_pathogenic	0.9948	pathogenic	-2.206	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/S	0.9713	likely_pathogenic	0.9754	pathogenic	-3.203	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/T	0.9333	likely_pathogenic	0.939	pathogenic	-2.773	Highly Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9995	pathogenic	-1.835	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
V/Y	0.9962	likely_pathogenic	0.9965	pathogenic	-1.758	Destabilizing	1.0	D	0.738	prob.delet.	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.