TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29572	88939;88940;88941	chr2:178554633;178554632;178554631	chr2:179419360;179419359;179419358
N2AB	27931	84016;84017;84018	chr2:178554633;178554632;178554631	chr2:179419360;179419359;179419358
N2A	27004	81235;81236;81237	chr2:178554633;178554632;178554631	chr2:179419360;179419359;179419358
N2B	20507	61744;61745;61746	chr2:178554633;178554632;178554631	chr2:179419360;179419359;179419358
Novex-1	20632	62119;62120;62121	chr2:178554633;178554632;178554631	chr2:179419360;179419359;179419358
Novex-2	20699	62320;62321;62322	chr2:178554633;178554632;178554631	chr2:179419360;179419359;179419358
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-103
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.0916
• 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
E/D	rs982929672	None	0.999	N	0.683	0.259	0.268660756437	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs982929672	None	0.999	N	0.683	0.259	0.268660756437	gnomAD-4.0.0	2.56181E-06	None	None	None	None	N	None	3.38123E-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
E/A	0.9071	likely_pathogenic	0.9184	pathogenic	-1.952	Destabilizing	0.999	D	0.747	deleterious	N	0.518897601	None	None	N
E/C	0.9894	likely_pathogenic	0.9896	pathogenic	-0.951	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/D	0.8037	likely_pathogenic	0.7895	pathogenic	-1.729	Destabilizing	0.999	D	0.683	prob.neutral	N	0.489525946	None	None	N
E/F	0.9958	likely_pathogenic	0.9963	pathogenic	-1.621	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
E/G	0.9216	likely_pathogenic	0.9265	pathogenic	-2.335	Highly Destabilizing	1.0	D	0.797	deleterious	D	0.538611699	None	None	N
E/H	0.9796	likely_pathogenic	0.9802	pathogenic	-1.429	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/I	0.9908	likely_pathogenic	0.9917	pathogenic	-0.838	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
E/K	0.9577	likely_pathogenic	0.9603	pathogenic	-1.759	Destabilizing	0.999	D	0.691	prob.neutral	D	0.524213519	None	None	N
E/L	0.9841	likely_pathogenic	0.9865	pathogenic	-0.838	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/M	0.9784	likely_pathogenic	0.9806	pathogenic	-0.032	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/N	0.9771	likely_pathogenic	0.9757	pathogenic	-1.924	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-1.198	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Q	0.6317	likely_pathogenic	0.6303	pathogenic	-1.623	Destabilizing	1.0	D	0.774	deleterious	N	0.500914548	None	None	N
E/R	0.9686	likely_pathogenic	0.971	pathogenic	-1.558	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/S	0.8958	likely_pathogenic	0.9039	pathogenic	-2.626	Highly Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/T	0.9728	likely_pathogenic	0.9734	pathogenic	-2.253	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/V	0.9717	likely_pathogenic	0.974	pathogenic	-1.198	Destabilizing	1.0	D	0.792	deleterious	D	0.526241435	None	None	N
E/W	0.9967	likely_pathogenic	0.9971	pathogenic	-1.666	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/Y	0.9918	likely_pathogenic	0.9929	pathogenic	-1.442	Destabilizing	1.0	D	0.851	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.