TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24664	74215;74216;74217	chr2:178572142;178572141;178572140	chr2:179436869;179436868;179436867
N2AB	23023	69292;69293;69294	chr2:178572142;178572141;178572140	chr2:179436869;179436868;179436867
N2A	22096	66511;66512;66513	chr2:178572142;178572141;178572140	chr2:179436869;179436868;179436867
N2B	15599	47020;47021;47022	chr2:178572142;178572141;178572140	chr2:179436869;179436868;179436867
Novex-1	15724	47395;47396;47397	chr2:178572142;178572141;178572140	chr2:179436869;179436868;179436867
Novex-2	15791	47596;47597;47598	chr2:178572142;178572141;178572140	chr2:179436869;179436868;179436867
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-67
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.2675
• 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/G	rs928815429	None	None	N	0.117	0.124	0.180583059064	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/G	rs928815429	None	None	N	0.117	0.124	0.180583059064	gnomAD-4.0.0	6.57531E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47072E-05	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	0.4257	ambiguous	0.4045	ambiguous	-0.753	Destabilizing	0.489	N	0.366	neutral	None	None	None	None	N
A/D	0.3909	ambiguous	0.3243	benign	-0.935	Destabilizing	0.092	N	0.345	neutral	N	0.42306984	None	None	N
A/E	0.3118	likely_benign	0.2451	benign	-1.057	Destabilizing	0.086	N	0.345	neutral	None	None	None	None	N
A/F	0.3244	likely_benign	0.2605	benign	-1.129	Destabilizing	0.639	D	0.377	neutral	None	None	None	None	N
A/G	0.1421	likely_benign	0.1241	benign	-0.866	Destabilizing	None	N	0.117	neutral	N	0.435884422	None	None	N
A/H	0.4418	ambiguous	0.3972	ambiguous	-0.872	Destabilizing	0.782	D	0.356	neutral	None	None	None	None	N
A/I	0.1779	likely_benign	0.1356	benign	-0.555	Destabilizing	0.08	N	0.337	neutral	None	None	None	None	N
A/K	0.5053	ambiguous	0.4267	ambiguous	-1.029	Destabilizing	0.201	N	0.339	neutral	None	None	None	None	N
A/L	0.1458	likely_benign	0.1155	benign	-0.555	Destabilizing	0.094	N	0.379	neutral	None	None	None	None	N
A/M	0.1491	likely_benign	0.1249	benign	-0.413	Destabilizing	0.639	D	0.351	neutral	None	None	None	None	N
A/N	0.1793	likely_benign	0.1536	benign	-0.646	Destabilizing	0.008	N	0.332	neutral	None	None	None	None	N
A/P	0.8458	likely_pathogenic	0.8077	pathogenic	-0.576	Destabilizing	0.171	N	0.355	neutral	N	0.477018968	None	None	N
A/Q	0.3261	likely_benign	0.2698	benign	-0.941	Destabilizing	0.639	D	0.378	neutral	None	None	None	None	N
A/R	0.4993	ambiguous	0.4217	ambiguous	-0.485	Destabilizing	0.639	D	0.387	neutral	None	None	None	None	N
A/S	0.0827	likely_benign	0.08	benign	-0.884	Destabilizing	None	N	0.137	neutral	N	0.358346358	None	None	N
A/T	0.0657	likely_benign	0.0648	benign	-0.93	Destabilizing	None	N	0.095	neutral	N	0.348033364	None	None	N
A/V	0.0978	likely_benign	0.0777	benign	-0.576	Destabilizing	None	N	0.145	neutral	N	0.385127528	None	None	N
A/W	0.7867	likely_pathogenic	0.731	pathogenic	-1.307	Destabilizing	0.976	D	0.425	neutral	None	None	None	None	N
A/Y	0.4599	ambiguous	0.4136	ambiguous	-0.972	Destabilizing	0.782	D	0.385	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.