TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17209	51850;51851;51852	chr2:178609798;178609797;178609796	chr2:179474525;179474524;179474523
N2AB	15568	46927;46928;46929	chr2:178609798;178609797;178609796	chr2:179474525;179474524;179474523
N2A	14641	44146;44147;44148	chr2:178609798;178609797;178609796	chr2:179474525;179474524;179474523
N2B	8144	24655;24656;24657	chr2:178609798;178609797;178609796	chr2:179474525;179474524;179474523
Novex-1	8269	25030;25031;25032	chr2:178609798;178609797;178609796	chr2:179474525;179474524;179474523
Novex-2	8336	25231;25232;25233	chr2:178609798;178609797;178609796	chr2:179474525;179474524;179474523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-13
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1585
• 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
A/T	rs1292930837	None	0.324	N	0.675	0.175	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs1292930837	None	0.324	N	0.675	0.175	None	gnomAD-4.0.0	6.82061E-06	None	None	None	None	N	None	6.68342E-05	0	None	0	0	None	0	0	5.08812E-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
A/C	0.3882	ambiguous	0.4418	ambiguous	-0.844	Destabilizing	0.944	D	0.707	prob.neutral	None	None	None	None	N
A/D	0.9234	likely_pathogenic	0.9439	pathogenic	-1.662	Destabilizing	0.818	D	0.783	deleterious	None	None	None	None	N
A/E	0.7917	likely_pathogenic	0.8268	pathogenic	-1.527	Destabilizing	0.492	N	0.767	deleterious	N	0.489158759	None	None	N
A/F	0.6228	likely_pathogenic	0.6937	pathogenic	-0.699	Destabilizing	0.69	D	0.801	deleterious	None	None	None	None	N
A/G	0.4765	ambiguous	0.4891	ambiguous	-1.333	Destabilizing	0.492	N	0.687	prob.neutral	N	0.500029114	None	None	N
A/H	0.896	likely_pathogenic	0.9284	pathogenic	-1.783	Destabilizing	0.981	D	0.807	deleterious	None	None	None	None	N
A/I	0.209	likely_benign	0.2333	benign	0.211	Stabilizing	0.043	N	0.668	neutral	None	None	None	None	N
A/K	0.9344	likely_pathogenic	0.9428	pathogenic	-1.185	Destabilizing	0.563	D	0.778	deleterious	None	None	None	None	N
A/L	0.2489	likely_benign	0.2999	benign	0.211	Stabilizing	0.116	N	0.645	neutral	None	None	None	None	N
A/M	0.3345	likely_benign	0.3905	ambiguous	0.116	Stabilizing	0.69	D	0.773	deleterious	None	None	None	None	N
A/N	0.8145	likely_pathogenic	0.8603	pathogenic	-1.229	Destabilizing	0.932	D	0.809	deleterious	None	None	None	None	N
A/P	0.8964	likely_pathogenic	0.9058	pathogenic	-0.113	Destabilizing	0.912	D	0.791	deleterious	N	0.489158759	None	None	N
A/Q	0.7871	likely_pathogenic	0.8246	pathogenic	-1.122	Destabilizing	0.932	D	0.788	deleterious	None	None	None	None	N
A/R	0.8916	likely_pathogenic	0.9056	pathogenic	-1.186	Destabilizing	0.818	D	0.793	deleterious	None	None	None	None	N
A/S	0.2142	likely_benign	0.2425	benign	-1.657	Destabilizing	0.324	N	0.679	prob.neutral	N	0.462241517	None	None	N
A/T	0.1437	likely_benign	0.157	benign	-1.393	Destabilizing	0.324	N	0.675	neutral	N	0.46591654	None	None	N
A/V	0.0897	likely_benign	0.0979	benign	-0.113	Destabilizing	None	N	0.3	neutral	N	0.285323106	None	None	N
A/W	0.9464	likely_pathogenic	0.963	pathogenic	-1.384	Destabilizing	0.981	D	0.819	deleterious	None	None	None	None	N
A/Y	0.829	likely_pathogenic	0.8712	pathogenic	-0.807	Destabilizing	0.818	D	0.812	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.