TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5554	16885;16886;16887	chr2:178732309;178732308;178732307	chr2:179597036;179597035;179597034
N2AB	5237	15934;15935;15936	chr2:178732309;178732308;178732307	chr2:179597036;179597035;179597034
N2A	4310	13153;13154;13155	chr2:178732309;178732308;178732307	chr2:179597036;179597035;179597034
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-39
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.6811
• 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/M	rs2080687572	None	1.0	N	0.605	0.228	0.352693368174	gnomAD-4.0.0	1.59845E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.44005E-05	0
L/V	None	None	0.999	N	0.508	0.229	0.241664281697	gnomAD-4.0.0	1.59846E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.42601E-04	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
L/A	0.2869	likely_benign	0.2838	benign	-0.954	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
L/C	0.4255	ambiguous	0.4149	ambiguous	-0.803	Destabilizing	1.0	D	0.569	neutral	None	None	None	None	I
L/D	0.5788	likely_pathogenic	0.5633	ambiguous	-0.307	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
L/E	0.3145	likely_benign	0.297	benign	-0.339	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
L/F	0.1101	likely_benign	0.1034	benign	-0.616	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	I
L/G	0.5045	ambiguous	0.5043	ambiguous	-1.196	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
L/H	0.1764	likely_benign	0.1663	benign	-0.318	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
L/I	0.0771	likely_benign	0.0707	benign	-0.402	Destabilizing	0.999	D	0.473	neutral	None	None	None	None	I
L/K	0.2451	likely_benign	0.2238	benign	-0.67	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
L/M	0.1116	likely_benign	0.1138	benign	-0.504	Destabilizing	1.0	D	0.605	neutral	N	0.520975681	None	None	I
L/N	0.3136	likely_benign	0.3043	benign	-0.584	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
L/P	0.3545	ambiguous	0.3451	ambiguous	-0.553	Destabilizing	1.0	D	0.671	neutral	N	0.494264385	None	None	I
L/Q	0.1436	likely_benign	0.1382	benign	-0.73	Destabilizing	1.0	D	0.654	neutral	N	0.481387142	None	None	I
L/R	0.1679	likely_benign	0.1834	benign	-0.119	Destabilizing	1.0	D	0.68	prob.neutral	N	0.494885158	None	None	I
L/S	0.2906	likely_benign	0.2786	benign	-1.115	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
L/T	0.2232	likely_benign	0.2126	benign	-1.03	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	I
L/V	0.086	likely_benign	0.0819	benign	-0.553	Destabilizing	0.999	D	0.508	neutral	N	0.413786714	None	None	I
L/W	0.1929	likely_benign	0.1913	benign	-0.66	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
L/Y	0.2352	likely_benign	0.2262	benign	-0.433	Destabilizing	1.0	D	0.628	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.