TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27241	81946;81947;81948	chr2:178564411;178564410;178564409	chr2:179429138;179429137;179429136
N2AB	25600	77023;77024;77025	chr2:178564411;178564410;178564409	chr2:179429138;179429137;179429136
N2A	24673	74242;74243;74244	chr2:178564411;178564410;178564409	chr2:179429138;179429137;179429136
N2B	18176	54751;54752;54753	chr2:178564411;178564410;178564409	chr2:179429138;179429137;179429136
Novex-1	18301	55126;55127;55128	chr2:178564411;178564410;178564409	chr2:179429138;179429137;179429136
Novex-2	18368	55327;55328;55329	chr2:178564411;178564410;178564409	chr2:179429138;179429137;179429136
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: Fn3-86
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.091
• 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/H	rs773476805	-2.588	1.0	D	0.846	0.826	0.765320684573	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
Y/H	rs773476805	-2.588	1.0	D	0.846	0.826	0.765320684573	gnomAD-4.0.0	3.18443E-06	None	None	None	None	N	None	0	4.57875E-05	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
Y/A	0.9937	likely_pathogenic	0.9909	pathogenic	-3.292	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/C	0.882	likely_pathogenic	0.816	pathogenic	-1.687	Destabilizing	1.0	D	0.881	deleterious	D	0.656684369	None	None	N
Y/D	0.9951	likely_pathogenic	0.9924	pathogenic	-3.734	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.694062878	None	None	N
Y/E	0.998	likely_pathogenic	0.9971	pathogenic	-3.517	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/F	0.3202	likely_benign	0.2915	benign	-1.3	Destabilizing	0.999	D	0.757	deleterious	D	0.634669806	None	None	N
Y/G	0.9812	likely_pathogenic	0.9764	pathogenic	-3.698	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/H	0.96	likely_pathogenic	0.9487	pathogenic	-2.455	Highly Destabilizing	1.0	D	0.846	deleterious	D	0.678043517	None	None	N
Y/I	0.9701	likely_pathogenic	0.9588	pathogenic	-1.92	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/K	0.9977	likely_pathogenic	0.9966	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/L	0.9517	likely_pathogenic	0.942	pathogenic	-1.92	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
Y/M	0.9784	likely_pathogenic	0.9722	pathogenic	-1.589	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/N	0.9602	likely_pathogenic	0.9449	pathogenic	-3.162	Highly Destabilizing	1.0	D	0.88	deleterious	D	0.693861074	None	None	N
Y/P	0.9989	likely_pathogenic	0.9986	pathogenic	-2.396	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
Y/Q	0.9963	likely_pathogenic	0.9947	pathogenic	-2.889	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/R	0.9924	likely_pathogenic	0.9897	pathogenic	-2.146	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/S	0.9769	likely_pathogenic	0.967	pathogenic	-3.434	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.694062878	None	None	N
Y/T	0.9915	likely_pathogenic	0.9873	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/V	0.9358	likely_pathogenic	0.9154	pathogenic	-2.396	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/W	0.8171	likely_pathogenic	0.7971	pathogenic	-0.59	Destabilizing	1.0	D	0.827	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.