TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22159	66700;66701;66702	chr2:178581793;178581792;178581791	chr2:179446520;179446519;179446518
N2AB	20518	61777;61778;61779	chr2:178581793;178581792;178581791	chr2:179446520;179446519;179446518
N2A	19591	58996;58997;58998	chr2:178581793;178581792;178581791	chr2:179446520;179446519;179446518
N2B	13094	39505;39506;39507	chr2:178581793;178581792;178581791	chr2:179446520;179446519;179446518
Novex-1	13219	39880;39881;39882	chr2:178581793;178581792;178581791	chr2:179446520;179446519;179446518
Novex-2	13286	40081;40082;40083	chr2:178581793;178581792;178581791	chr2:179446520;179446519;179446518
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-49
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2821
• 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
P/S	rs1471770452	-1.325	1.0	N	0.843	0.41	0.361160317528	gnomAD-2.1.1	4.43E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.82E-06	0
P/S	rs1471770452	-1.325	1.0	N	0.843	0.41	0.361160317528	gnomAD-4.0.0	3.27065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9244E-06	0	3.09521E-05

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
P/A	0.1854	likely_benign	0.194	benign	-1.181	Destabilizing	1.0	D	0.823	deleterious	N	0.50060233	None	None	N
P/C	0.7811	likely_pathogenic	0.8146	pathogenic	-0.985	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/D	0.9518	likely_pathogenic	0.97	pathogenic	-1.539	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/E	0.8161	likely_pathogenic	0.8587	pathogenic	-1.613	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/F	0.8909	likely_pathogenic	0.9175	pathogenic	-1.359	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
P/G	0.7754	likely_pathogenic	0.8288	pathogenic	-1.383	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/H	0.6827	likely_pathogenic	0.757	pathogenic	-0.886	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/I	0.7478	likely_pathogenic	0.7917	pathogenic	-0.752	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
P/K	0.7684	likely_pathogenic	0.8279	pathogenic	-0.805	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/L	0.4905	ambiguous	0.581	pathogenic	-0.752	Destabilizing	1.0	D	0.887	deleterious	D	0.531547807	None	None	N
P/M	0.7019	likely_pathogenic	0.7505	pathogenic	-0.521	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
P/N	0.8602	likely_pathogenic	0.8998	pathogenic	-0.644	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/Q	0.5382	ambiguous	0.6258	pathogenic	-0.993	Destabilizing	1.0	D	0.855	deleterious	N	0.501629493	None	None	N
P/R	0.628	likely_pathogenic	0.7185	pathogenic	-0.23	Destabilizing	1.0	D	0.898	deleterious	N	0.509542759	None	None	N
P/S	0.4205	ambiguous	0.4921	ambiguous	-1.028	Destabilizing	1.0	D	0.843	deleterious	N	0.479486314	None	None	N
P/T	0.5072	ambiguous	0.5784	pathogenic	-1.012	Destabilizing	1.0	D	0.843	deleterious	N	0.512936573	None	None	N
P/V	0.6053	likely_pathogenic	0.658	pathogenic	-0.863	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/W	0.9651	likely_pathogenic	0.9762	pathogenic	-1.432	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
P/Y	0.9051	likely_pathogenic	0.9305	pathogenic	-1.101	Destabilizing	1.0	D	0.917	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.