TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20242	60949;60950;60951	chr2:178591001;178591000;178590999	chr2:179455728;179455727;179455726
N2AB	18601	56026;56027;56028	chr2:178591001;178591000;178590999	chr2:179455728;179455727;179455726
N2A	17674	53245;53246;53247	chr2:178591001;178591000;178590999	chr2:179455728;179455727;179455726
N2B	11177	33754;33755;33756	chr2:178591001;178591000;178590999	chr2:179455728;179455727;179455726
Novex-1	11302	34129;34130;34131	chr2:178591001;178591000;178590999	chr2:179455728;179455727;179455726
Novex-2	11369	34330;34331;34332	chr2:178591001;178591000;178590999	chr2:179455728;179455727;179455726
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-34
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0727
• 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
Y/C	None	None	1.0	D	0.865	0.882	0.930883039408	gnomAD-4.0.0	1.5919E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85977E-06	0	0
Y/H	None	None	1.0	D	0.823	0.868	0.847466415278	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
Y/A	0.9928	likely_pathogenic	0.9943	pathogenic	-3.294	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/C	0.9685	likely_pathogenic	0.9706	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.659934674	None	None	N
Y/D	0.9886	likely_pathogenic	0.9914	pathogenic	-3.561	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.675954035	None	None	N
Y/E	0.997	likely_pathogenic	0.9976	pathogenic	-3.393	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/F	0.413	ambiguous	0.3846	ambiguous	-1.097	Destabilizing	0.999	D	0.74	deleterious	D	0.642099075	None	None	N
Y/G	0.9804	likely_pathogenic	0.9855	pathogenic	-3.682	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/H	0.9777	likely_pathogenic	0.9778	pathogenic	-2.123	Highly Destabilizing	1.0	D	0.823	deleterious	D	0.675954035	None	None	N
Y/I	0.9652	likely_pathogenic	0.9662	pathogenic	-2.005	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/K	0.9969	likely_pathogenic	0.9972	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/L	0.9527	likely_pathogenic	0.9518	pathogenic	-2.005	Highly Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
Y/M	0.9798	likely_pathogenic	0.9798	pathogenic	-1.767	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/N	0.9485	likely_pathogenic	0.9562	pathogenic	-2.873	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.675752231	None	None	N
Y/P	0.9986	likely_pathogenic	0.9991	pathogenic	-2.449	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
Y/Q	0.9973	likely_pathogenic	0.9978	pathogenic	-2.72	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/R	0.9932	likely_pathogenic	0.994	pathogenic	-1.79	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/S	0.9824	likely_pathogenic	0.9859	pathogenic	-3.241	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.643915313	None	None	N
Y/T	0.9891	likely_pathogenic	0.9919	pathogenic	-2.965	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/V	0.9276	likely_pathogenic	0.9335	pathogenic	-2.449	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/W	0.9173	likely_pathogenic	0.9058	pathogenic	-0.463	Destabilizing	1.0	D	0.804	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.