TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22796	68611;68612;68613	chr2:178578129;178578128;178578127	chr2:179442856;179442855;179442854
N2AB	21155	63688;63689;63690	chr2:178578129;178578128;178578127	chr2:179442856;179442855;179442854
N2A	20228	60907;60908;60909	chr2:178578129;178578128;178578127	chr2:179442856;179442855;179442854
N2B	13731	41416;41417;41418	chr2:178578129;178578128;178578127	chr2:179442856;179442855;179442854
Novex-1	13856	41791;41792;41793	chr2:178578129;178578128;178578127	chr2:179442856;179442855;179442854
Novex-2	13923	41992;41993;41994	chr2:178578129;178578128;178578127	chr2:179442856;179442855;179442854
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-53
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.644
• Predicted PPI site: I

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/I	rs756135570	0.23	0.032	N	0.201	0.158	0.254244900254	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	8.91E-06	0
T/I	rs756135570	0.23	0.032	N	0.201	0.158	0.254244900254	gnomAD-4.0.0	3.18521E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86076E-06	1.43332E-05	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	0.082	likely_benign	0.0859	benign	-0.257	Destabilizing	0.489	N	0.373	neutral	N	0.493391143	None	None	I
T/C	0.3793	ambiguous	0.3988	ambiguous	-0.205	Destabilizing	0.998	D	0.43	neutral	None	None	None	None	I
T/D	0.4989	ambiguous	0.535	ambiguous	0.074	Stabilizing	0.915	D	0.387	neutral	None	None	None	None	I
T/E	0.4217	ambiguous	0.4389	ambiguous	0.001	Stabilizing	0.956	D	0.387	neutral	None	None	None	None	I
T/F	0.2244	likely_benign	0.2228	benign	-0.767	Destabilizing	0.956	D	0.499	neutral	None	None	None	None	I
T/G	0.2058	likely_benign	0.2401	benign	-0.379	Destabilizing	0.86	D	0.455	neutral	None	None	None	None	I
T/H	0.2894	likely_benign	0.3006	benign	-0.566	Destabilizing	0.994	D	0.496	neutral	None	None	None	None	I
T/I	0.1349	likely_benign	0.1236	benign	-0.054	Destabilizing	0.032	N	0.201	neutral	N	0.473498661	None	None	I
T/K	0.4074	ambiguous	0.4144	ambiguous	-0.335	Destabilizing	0.956	D	0.381	neutral	None	None	None	None	I
T/L	0.0891	likely_benign	0.0884	benign	-0.054	Destabilizing	0.559	D	0.409	neutral	None	None	None	None	I
T/M	0.075	likely_benign	0.0712	benign	-0.051	Destabilizing	0.956	D	0.393	neutral	None	None	None	None	I
T/N	0.1018	likely_benign	0.1076	benign	-0.077	Destabilizing	0.125	N	0.149	neutral	N	0.517518797	None	None	I
T/P	0.2739	likely_benign	0.2918	benign	-0.094	Destabilizing	0.99	D	0.396	neutral	N	0.476832379	None	None	I
T/Q	0.2597	likely_benign	0.272	benign	-0.276	Destabilizing	0.978	D	0.382	neutral	None	None	None	None	I
T/R	0.3937	ambiguous	0.3938	ambiguous	-0.029	Destabilizing	0.978	D	0.396	neutral	None	None	None	None	I
T/S	0.1012	likely_benign	0.1062	benign	-0.251	Destabilizing	0.822	D	0.388	neutral	N	0.472725082	None	None	I
T/V	0.109	likely_benign	0.1052	benign	-0.094	Destabilizing	0.019	N	0.147	neutral	None	None	None	None	I
T/W	0.6058	likely_pathogenic	0.6245	pathogenic	-0.832	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	I
T/Y	0.2475	likely_benign	0.2524	benign	-0.533	Destabilizing	0.978	D	0.499	neutral	None	None	None	None	I

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.