TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23851	71776;71777;71778	chr2:178574581;178574580;178574579	chr2:179439308;179439307;179439306
N2AB	22210	66853;66854;66855	chr2:178574581;178574580;178574579	chr2:179439308;179439307;179439306
N2A	21283	64072;64073;64074	chr2:178574581;178574580;178574579	chr2:179439308;179439307;179439306
N2B	14786	44581;44582;44583	chr2:178574581;178574580;178574579	chr2:179439308;179439307;179439306
Novex-1	14911	44956;44957;44958	chr2:178574581;178574580;178574579	chr2:179439308;179439307;179439306
Novex-2	14978	45157;45158;45159	chr2:178574581;178574580;178574579	chr2:179439308;179439307;179439306
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-61
• Domain position: 26
• Structural Position: 28
• Q(SASA): 1.2544
• 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
L/P	None	None	0.927	N	0.387	0.263	0.655717221024	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.1335	likely_benign	0.1501	benign	-0.449	Destabilizing	0.329	N	0.307	neutral	None	None	None	None	I
L/C	0.422	ambiguous	0.4339	ambiguous	-0.854	Destabilizing	0.981	D	0.335	neutral	None	None	None	None	I
L/D	0.4804	ambiguous	0.5149	ambiguous	-0.207	Destabilizing	0.704	D	0.417	neutral	None	None	None	None	I
L/E	0.2762	likely_benign	0.3138	benign	-0.301	Destabilizing	0.704	D	0.419	neutral	None	None	None	None	I
L/F	0.1278	likely_benign	0.1438	benign	-0.667	Destabilizing	0.006	N	0.202	neutral	N	0.502818703	None	None	I
L/G	0.3132	likely_benign	0.3403	ambiguous	-0.522	Destabilizing	0.704	D	0.459	neutral	None	None	None	None	I
L/H	0.1958	likely_benign	0.2215	benign	0.035	Stabilizing	0.993	D	0.301	neutral	N	0.449197649	None	None	I
L/I	0.0704	likely_benign	0.075	benign	-0.372	Destabilizing	0.002	N	0.135	neutral	N	0.40402272	None	None	I
L/K	0.2425	likely_benign	0.2558	benign	-0.345	Destabilizing	0.704	D	0.454	neutral	None	None	None	None	I
L/M	0.1019	likely_benign	0.107	benign	-0.651	Destabilizing	0.893	D	0.357	neutral	None	None	None	None	I
L/N	0.2125	likely_benign	0.2317	benign	-0.215	Destabilizing	0.893	D	0.391	neutral	None	None	None	None	I
L/P	0.144	likely_benign	0.169	benign	-0.372	Destabilizing	0.927	D	0.387	neutral	N	0.430033098	None	None	I
L/Q	0.1274	likely_benign	0.1415	benign	-0.379	Destabilizing	0.944	D	0.381	neutral	None	None	None	None	I
L/R	0.202	likely_benign	0.2132	benign	0.071	Stabilizing	0.927	D	0.399	neutral	N	0.42491528	None	None	I
L/S	0.1483	likely_benign	0.1712	benign	-0.59	Destabilizing	0.037	N	0.19	neutral	None	None	None	None	I
L/T	0.1388	likely_benign	0.159	benign	-0.589	Destabilizing	0.329	N	0.379	neutral	None	None	None	None	I
L/V	0.0646	likely_benign	0.0708	benign	-0.372	Destabilizing	0.002	N	0.132	neutral	N	0.370640865	None	None	I
L/W	0.2975	likely_benign	0.2914	benign	-0.681	Destabilizing	0.995	D	0.323	neutral	None	None	None	None	I
L/Y	0.2964	likely_benign	0.3057	benign	-0.458	Destabilizing	0.807	D	0.415	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.