TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14101	42526;42527;42528	chr2:178634480;178634479;178634478	chr2:179499207;179499206;179499205
N2AB	12460	37603;37604;37605	chr2:178634480;178634479;178634478	chr2:179499207;179499206;179499205
N2A	11533	34822;34823;34824	chr2:178634480;178634479;178634478	chr2:179499207;179499206;179499205
N2B	5036	15331;15332;15333	chr2:178634480;178634479;178634478	chr2:179499207;179499206;179499205
Novex-1	5161	15706;15707;15708	chr2:178634480;178634479;178634478	chr2:179499207;179499206;179499205
Novex-2	5228	15907;15908;15909	chr2:178634480;178634479;178634478	chr2:179499207;179499206;179499205
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-91
• Domain position: 48
• Structural Position: 125
• Q(SASA): 0.4005
• 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
I/T	rs776663967	-0.947	0.822	N	0.539	0.251	0.687263012116	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	8.92E-06	0
I/T	rs776663967	-0.947	0.822	N	0.539	0.251	0.687263012116	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
I/A	0.7809	likely_pathogenic	0.6881	pathogenic	-1.244	Destabilizing	0.86	D	0.519	neutral	None	None	None	None	N
I/C	0.9723	likely_pathogenic	0.9431	pathogenic	-0.688	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
I/D	0.9771	likely_pathogenic	0.9543	pathogenic	-0.978	Destabilizing	0.978	D	0.671	neutral	None	None	None	None	N
I/E	0.9237	likely_pathogenic	0.8501	pathogenic	-1.036	Destabilizing	0.956	D	0.618	neutral	None	None	None	None	N
I/F	0.4083	ambiguous	0.3091	benign	-0.997	Destabilizing	0.942	D	0.535	neutral	N	0.5079464	None	None	N
I/G	0.9695	likely_pathogenic	0.9536	pathogenic	-1.49	Destabilizing	0.978	D	0.638	neutral	None	None	None	None	N
I/H	0.8894	likely_pathogenic	0.7757	pathogenic	-0.73	Destabilizing	0.998	D	0.664	neutral	None	None	None	None	N
I/K	0.8533	likely_pathogenic	0.696	pathogenic	-0.935	Destabilizing	0.076	N	0.392	neutral	None	None	None	None	N
I/L	0.3001	likely_benign	0.2328	benign	-0.675	Destabilizing	0.006	N	0.119	neutral	N	0.487761844	None	None	N
I/M	0.2737	likely_benign	0.2227	benign	-0.478	Destabilizing	0.976	D	0.565	neutral	D	0.540095777	None	None	N
I/N	0.8591	likely_pathogenic	0.7591	pathogenic	-0.668	Destabilizing	0.97	D	0.668	neutral	D	0.523636015	None	None	N
I/P	0.9882	likely_pathogenic	0.9847	pathogenic	-0.832	Destabilizing	0.993	D	0.671	neutral	None	None	None	None	N
I/Q	0.8499	likely_pathogenic	0.7391	pathogenic	-0.917	Destabilizing	0.956	D	0.669	neutral	None	None	None	None	N
I/R	0.7668	likely_pathogenic	0.5983	pathogenic	-0.253	Destabilizing	0.915	D	0.667	neutral	None	None	None	None	N
I/S	0.7792	likely_pathogenic	0.6873	pathogenic	-1.129	Destabilizing	0.822	D	0.579	neutral	N	0.492462267	None	None	N
I/T	0.5804	likely_pathogenic	0.4278	ambiguous	-1.083	Destabilizing	0.822	D	0.539	neutral	N	0.483914177	None	None	N
I/V	0.2417	likely_benign	0.1639	benign	-0.832	Destabilizing	0.489	N	0.315	neutral	N	0.500527855	None	None	N
I/W	0.9465	likely_pathogenic	0.9066	pathogenic	-1.041	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
I/Y	0.8353	likely_pathogenic	0.7503	pathogenic	-0.832	Destabilizing	0.978	D	0.611	neutral	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.