TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23102	69529;69530;69531	chr2:178577031;178577030;178577029	chr2:179441758;179441757;179441756
N2AB	21461	64606;64607;64608	chr2:178577031;178577030;178577029	chr2:179441758;179441757;179441756
N2A	20534	61825;61826;61827	chr2:178577031;178577030;178577029	chr2:179441758;179441757;179441756
N2B	14037	42334;42335;42336	chr2:178577031;178577030;178577029	chr2:179441758;179441757;179441756
Novex-1	14162	42709;42710;42711	chr2:178577031;178577030;178577029	chr2:179441758;179441757;179441756
Novex-2	14229	42910;42911;42912	chr2:178577031;178577030;178577029	chr2:179441758;179441757;179441756
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-55
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.455
• 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
T/S	rs1372466257	-0.61	None	N	0.109	0.098	0.12205267543	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	1.1147E-04	None	0	None	0	0	0
T/S	rs1372466257	-0.61	None	N	0.109	0.098	0.12205267543	gnomAD-4.0.0	1.59186E-06	None	None	None	None	N	None	0	0	None	0	2.77408E-05	None	0	0	0	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
T/A	0.0894	likely_benign	0.0798	benign	-0.414	Destabilizing	None	N	0.107	neutral	N	0.477955831	None	None	N
T/C	0.3912	ambiguous	0.3069	benign	-0.334	Destabilizing	0.001	N	0.255	neutral	None	None	None	None	N
T/D	0.4457	ambiguous	0.4319	ambiguous	0.145	Stabilizing	0.104	N	0.395	neutral	None	None	None	None	N
T/E	0.3551	ambiguous	0.366	ambiguous	0.129	Stabilizing	0.055	N	0.377	neutral	None	None	None	None	N
T/F	0.2954	likely_benign	0.2637	benign	-0.568	Destabilizing	0.667	D	0.541	neutral	None	None	None	None	N
T/G	0.1656	likely_benign	0.1351	benign	-0.638	Destabilizing	0.055	N	0.329	neutral	None	None	None	None	N
T/H	0.2787	likely_benign	0.2502	benign	-0.823	Destabilizing	0.667	D	0.471	neutral	None	None	None	None	N
T/I	0.24	likely_benign	0.2055	benign	0.075	Stabilizing	0.175	N	0.426	neutral	N	0.482514961	None	None	N
T/K	0.2316	likely_benign	0.2606	benign	-0.516	Destabilizing	0.055	N	0.373	neutral	None	None	None	None	N
T/L	0.1077	likely_benign	0.0969	benign	0.075	Stabilizing	0.055	N	0.373	neutral	None	None	None	None	N
T/M	0.1105	likely_benign	0.0999	benign	0.045	Stabilizing	0.667	D	0.453	neutral	None	None	None	None	N
T/N	0.1286	likely_benign	0.1183	benign	-0.395	Destabilizing	0.175	N	0.259	neutral	N	0.517828228	None	None	N
T/P	0.1208	likely_benign	0.1128	benign	-0.055	Destabilizing	None	N	0.192	neutral	N	0.480740535	None	None	N
T/Q	0.2267	likely_benign	0.2199	benign	-0.505	Destabilizing	0.011	N	0.246	neutral	None	None	None	None	N
T/R	0.2196	likely_benign	0.2382	benign	-0.287	Destabilizing	0.22	N	0.429	neutral	None	None	None	None	N
T/S	0.0951	likely_benign	0.0848	benign	-0.634	Destabilizing	None	N	0.109	neutral	N	0.472709227	None	None	N
T/V	0.1455	likely_benign	0.1247	benign	-0.055	Destabilizing	0.055	N	0.264	neutral	None	None	None	None	N
T/W	0.5727	likely_pathogenic	0.531	ambiguous	-0.591	Destabilizing	0.958	D	0.479	neutral	None	None	None	None	N
T/Y	0.3072	likely_benign	0.2891	benign	-0.323	Destabilizing	0.859	D	0.507	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.