TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16900	50923;50924;50925	chr2:178611531;178611530;178611529	chr2:179476258;179476257;179476256
N2AB	15259	46000;46001;46002	chr2:178611531;178611530;178611529	chr2:179476258;179476257;179476256
N2A	14332	43219;43220;43221	chr2:178611531;178611530;178611529	chr2:179476258;179476257;179476256
N2B	7835	23728;23729;23730	chr2:178611531;178611530;178611529	chr2:179476258;179476257;179476256
Novex-1	7960	24103;24104;24105	chr2:178611531;178611530;178611529	chr2:179476258;179476257;179476256
Novex-2	8027	24304;24305;24306	chr2:178611531;178611530;178611529	chr2:179476258;179476257;179476256
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-11
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.3657
• 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
M/I	None	None	0.985	N	0.514	0.344	0.41921206133	gnomAD-4.0.0	6.84504E-07	None	None	None	None	I	None	0	0	None	0	2.52423E-05	None	0	0	0	0	0
M/V	rs2056323047	None	0.985	N	0.411	0.356	0.383256108077	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
M/V	rs2056323047	None	0.985	N	0.411	0.356	0.383256108077	gnomAD-4.0.0	6.57929E-06	None	None	None	None	I	None	2.41324E-05	0	None	0	0	None	0	0	0	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
M/A	0.7079	likely_pathogenic	0.7617	pathogenic	-1.778	Destabilizing	0.989	D	0.518	neutral	None	None	None	None	I
M/C	0.8025	likely_pathogenic	0.8682	pathogenic	-1.067	Destabilizing	1.0	D	0.573	neutral	None	None	None	None	I
M/D	0.926	likely_pathogenic	0.9431	pathogenic	-0.606	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	I
M/E	0.6576	likely_pathogenic	0.6979	pathogenic	-0.584	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	I
M/F	0.443	ambiguous	0.5185	ambiguous	-0.777	Destabilizing	0.999	D	0.48	neutral	None	None	None	None	I
M/G	0.8327	likely_pathogenic	0.8721	pathogenic	-2.068	Highly Destabilizing	0.995	D	0.523	neutral	None	None	None	None	I
M/H	0.6686	likely_pathogenic	0.6977	pathogenic	-1.002	Destabilizing	1.0	D	0.61	neutral	None	None	None	None	I
M/I	0.5167	ambiguous	0.5387	ambiguous	-1.03	Destabilizing	0.985	D	0.514	neutral	N	0.459778709	None	None	I
M/K	0.3767	ambiguous	0.4048	ambiguous	-0.671	Destabilizing	0.994	D	0.513	neutral	N	0.459795224	None	None	I
M/L	0.1746	likely_benign	0.1806	benign	-1.03	Destabilizing	0.927	D	0.239	neutral	N	0.452242206	None	None	I
M/N	0.6661	likely_pathogenic	0.7078	pathogenic	-0.511	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	I
M/P	0.9842	likely_pathogenic	0.984	pathogenic	-1.254	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	I
M/Q	0.3122	likely_benign	0.3557	ambiguous	-0.616	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	I
M/R	0.4319	ambiguous	0.4497	ambiguous	-0.073	Destabilizing	0.998	D	0.526	neutral	N	0.469351101	None	None	I
M/S	0.6741	likely_pathogenic	0.7234	pathogenic	-1.091	Destabilizing	0.995	D	0.491	neutral	None	None	None	None	I
M/T	0.5463	ambiguous	0.5743	pathogenic	-0.967	Destabilizing	0.994	D	0.514	neutral	N	0.455230888	None	None	I
M/V	0.1813	likely_benign	0.188	benign	-1.254	Destabilizing	0.985	D	0.411	neutral	N	0.448378468	None	None	I
M/W	0.7566	likely_pathogenic	0.805	pathogenic	-0.682	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	I
M/Y	0.6872	likely_pathogenic	0.7591	pathogenic	-0.747	Destabilizing	0.999	D	0.568	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.