TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28884	86875;86876;86877	chr2:178559482;178559481;178559480	chr2:179424209;179424208;179424207
N2AB	27243	81952;81953;81954	chr2:178559482;178559481;178559480	chr2:179424209;179424208;179424207
N2A	26316	79171;79172;79173	chr2:178559482;178559481;178559480	chr2:179424209;179424208;179424207
N2B	19819	59680;59681;59682	chr2:178559482;178559481;178559480	chr2:179424209;179424208;179424207
Novex-1	19944	60055;60056;60057	chr2:178559482;178559481;178559480	chr2:179424209;179424208;179424207
Novex-2	20011	60256;60257;60258	chr2:178559482;178559481;178559480	chr2:179424209;179424208;179424207
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-98
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2381
• 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
K/E	rs761832458	-1.915	0.994	N	0.627	0.315	0.344710718752	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/E	rs761832458	-1.915	0.994	N	0.627	0.315	0.344710718752	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs761832458	-1.915	0.994	N	0.627	0.315	0.344710718752	gnomAD-4.0.0	1.85921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69532E-06	1.09803E-05	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
K/A	0.9421	likely_pathogenic	0.9291	pathogenic	-1.366	Destabilizing	0.99	D	0.544	neutral	None	None	None	None	N
K/C	0.8513	likely_pathogenic	0.8454	pathogenic	-1.381	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.9967	likely_pathogenic	0.996	pathogenic	-2.28	Highly Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
K/E	0.9217	likely_pathogenic	0.8849	pathogenic	-1.945	Destabilizing	0.994	D	0.627	neutral	N	0.473027853	None	None	N
K/F	0.9637	likely_pathogenic	0.9542	pathogenic	-0.716	Destabilizing	0.994	D	0.685	prob.neutral	None	None	None	None	N
K/G	0.9714	likely_pathogenic	0.9666	pathogenic	-1.847	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
K/H	0.7893	likely_pathogenic	0.7867	pathogenic	-1.484	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
K/I	0.818	likely_pathogenic	0.7812	pathogenic	0.024	Stabilizing	0.015	N	0.587	neutral	N	0.419605461	None	None	N
K/L	0.7687	likely_pathogenic	0.745	pathogenic	0.024	Stabilizing	0.005	N	0.536	neutral	None	None	None	None	N
K/M	0.5605	ambiguous	0.502	ambiguous	-0.402	Destabilizing	0.981	D	0.62	neutral	None	None	None	None	N
K/N	0.9793	likely_pathogenic	0.9736	pathogenic	-1.952	Destabilizing	1.0	D	0.589	neutral	N	0.484548742	None	None	N
K/P	0.9989	likely_pathogenic	0.9988	pathogenic	-0.423	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
K/Q	0.5559	ambiguous	0.4916	ambiguous	-1.509	Destabilizing	0.996	D	0.623	neutral	N	0.495874088	None	None	N
K/R	0.1436	likely_benign	0.1413	benign	-0.727	Destabilizing	0.991	D	0.614	neutral	N	0.411948769	None	None	N
K/S	0.9673	likely_pathogenic	0.9601	pathogenic	-2.383	Highly Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
K/T	0.8686	likely_pathogenic	0.8283	pathogenic	-1.783	Destabilizing	0.983	D	0.561	neutral	N	0.489620119	None	None	N
K/V	0.7743	likely_pathogenic	0.7378	pathogenic	-0.423	Destabilizing	0.496	N	0.583	neutral	None	None	None	None	N
K/W	0.9504	likely_pathogenic	0.9432	pathogenic	-0.808	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/Y	0.8693	likely_pathogenic	0.8638	pathogenic	-0.442	Destabilizing	0.992	D	0.657	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.