TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14082	42469;42470;42471	chr2:178634537;178634536;178634535	chr2:179499264;179499263;179499262
N2AB	12441	37546;37547;37548	chr2:178634537;178634536;178634535	chr2:179499264;179499263;179499262
N2A	11514	34765;34766;34767	chr2:178634537;178634536;178634535	chr2:179499264;179499263;179499262
N2B	5017	15274;15275;15276	chr2:178634537;178634536;178634535	chr2:179499264;179499263;179499262
Novex-1	5142	15649;15650;15651	chr2:178634537;178634536;178634535	chr2:179499264;179499263;179499262
Novex-2	5209	15850;15851;15852	chr2:178634537;178634536;178634535	chr2:179499264;179499263;179499262
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-91
• Domain position: 29
• Structural Position: 45
• Q(SASA): 0.895
• 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
N/K	rs907132563	None	0.044	N	0.154	0.144	0.0551355673512	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	1.31234E-04	0	0	0	None	0	0	1.47E-05	0	0
N/K	rs907132563	None	0.044	N	0.154	0.144	0.0551355673512	gnomAD-4.0.0	4.33938E-06	None	None	None	None	N	None	0	3.33656E-05	None	0	0	None	0	0	4.23898E-06	0	0
N/S	None	None	0.91	N	0.498	0.227	0.154104182512	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
N/A	0.2411	likely_benign	0.2506	benign	-0.088	Destabilizing	0.97	D	0.525	neutral	None	None	None	None	N
N/C	0.5511	ambiguous	0.5673	pathogenic	0.12	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
N/D	0.146	likely_benign	0.1786	benign	0.101	Stabilizing	0.98	D	0.511	neutral	N	0.480458023	None	None	N
N/E	0.4455	ambiguous	0.4727	ambiguous	0.057	Stabilizing	0.931	D	0.469	neutral	None	None	None	None	N
N/F	0.7836	likely_pathogenic	0.7883	pathogenic	-0.683	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
N/G	0.3221	likely_benign	0.3345	benign	-0.194	Destabilizing	0.985	D	0.473	neutral	None	None	None	None	N
N/H	0.1442	likely_benign	0.1651	benign	-0.171	Destabilizing	0.998	D	0.557	neutral	N	0.501101369	None	None	N
N/I	0.4252	ambiguous	0.4301	ambiguous	0.096	Stabilizing	0.998	D	0.637	neutral	N	0.492659572	None	None	N
N/K	0.3377	likely_benign	0.3568	ambiguous	0.114	Stabilizing	0.044	N	0.154	neutral	N	0.39727612	None	None	N
N/L	0.3994	ambiguous	0.4022	ambiguous	0.096	Stabilizing	0.985	D	0.551	neutral	None	None	None	None	N
N/M	0.512	ambiguous	0.5145	ambiguous	-0.027	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
N/P	0.4425	ambiguous	0.4647	ambiguous	0.058	Stabilizing	0.999	D	0.587	neutral	None	None	None	None	N
N/Q	0.4214	ambiguous	0.4285	ambiguous	-0.147	Destabilizing	0.97	D	0.503	neutral	None	None	None	None	N
N/R	0.4049	ambiguous	0.4368	ambiguous	0.199	Stabilizing	0.942	D	0.48	neutral	None	None	None	None	N
N/S	0.0846	likely_benign	0.0898	benign	0.019	Stabilizing	0.91	D	0.498	neutral	N	0.481201794	None	None	N
N/T	0.1702	likely_benign	0.1617	benign	0.089	Stabilizing	0.98	D	0.479	neutral	N	0.457926175	None	None	N
N/V	0.3639	ambiguous	0.3686	ambiguous	0.058	Stabilizing	0.996	D	0.556	neutral	None	None	None	None	N
N/W	0.9044	likely_pathogenic	0.9084	pathogenic	-0.837	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
N/Y	0.323	likely_benign	0.344	ambiguous	-0.495	Destabilizing	0.998	D	0.643	neutral	D	0.538763303	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.