TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31041	93346;93347;93348	chr2:178548505;178548504;178548503	chr2:179413232;179413231;179413230
N2AB	29400	88423;88424;88425	chr2:178548505;178548504;178548503	chr2:179413232;179413231;179413230
N2A	28473	85642;85643;85644	chr2:178548505;178548504;178548503	chr2:179413232;179413231;179413230
N2B	21976	66151;66152;66153	chr2:178548505;178548504;178548503	chr2:179413232;179413231;179413230
Novex-1	22101	66526;66527;66528	chr2:178548505;178548504;178548503	chr2:179413232;179413231;179413230
Novex-2	22168	66727;66728;66729	chr2:178548505;178548504;178548503	chr2:179413232;179413231;179413230
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: Fn3-114
• Domain position: 26
• Structural Position: 28
• Q(SASA): 1.1557
• 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/F	None	None	0.055	N	0.277	0.153	0.28492961333	gnomAD-4.0.0	6.84176E-07	None	None	None	None	I	None	0	0	None	0	2.51915E-05	None	0	0	0	0	0
L/I	rs1698098552	None	None	N	0.086	0.079	0.180583059064	gnomAD-4.0.0	6.84176E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99442E-07	0	0
L/V	None	None	None	N	0.105	0.08	0.20549828249	gnomAD-4.0.0	6.84176E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99442E-07	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	0.1399	likely_benign	0.1403	benign	-0.499	Destabilizing	0.007	N	0.206	neutral	None	None	None	None	I
L/C	0.4466	ambiguous	0.4466	ambiguous	-0.853	Destabilizing	0.628	D	0.25	neutral	None	None	None	None	I
L/D	0.4695	ambiguous	0.4613	ambiguous	-0.344	Destabilizing	0.038	N	0.317	neutral	None	None	None	None	I
L/E	0.2656	likely_benign	0.2529	benign	-0.433	Destabilizing	0.001	N	0.213	neutral	None	None	None	None	I
L/F	0.1344	likely_benign	0.1382	benign	-0.664	Destabilizing	0.055	N	0.277	neutral	N	0.504018896	None	None	I
L/G	0.3479	ambiguous	0.3425	ambiguous	-0.589	Destabilizing	0.031	N	0.273	neutral	None	None	None	None	I
L/H	0.2063	likely_benign	0.2034	benign	0.073	Stabilizing	0.295	N	0.241	neutral	N	0.498195999	None	None	I
L/I	0.0683	likely_benign	0.0761	benign	-0.377	Destabilizing	None	N	0.086	neutral	N	0.492641782	None	None	I
L/K	0.2424	likely_benign	0.2342	benign	-0.404	Destabilizing	0.016	N	0.236	neutral	None	None	None	None	I
L/M	0.0969	likely_benign	0.1032	benign	-0.699	Destabilizing	0.214	N	0.286	neutral	None	None	None	None	I
L/N	0.2108	likely_benign	0.2133	benign	-0.298	Destabilizing	0.072	N	0.367	neutral	None	None	None	None	I
L/P	0.2045	likely_benign	0.2028	benign	-0.392	Destabilizing	0.106	N	0.335	neutral	N	0.464074176	None	None	I
L/Q	0.1321	likely_benign	0.1246	benign	-0.471	Destabilizing	0.072	N	0.343	neutral	None	None	None	None	I
L/R	0.206	likely_benign	0.1948	benign	0.061	Stabilizing	None	N	0.211	neutral	N	0.51622793	None	None	I
L/S	0.1633	likely_benign	0.1616	benign	-0.657	Destabilizing	0.001	N	0.133	neutral	None	None	None	None	I
L/T	0.1432	likely_benign	0.1437	benign	-0.65	Destabilizing	None	N	0.16	neutral	None	None	None	None	I
L/V	0.0715	likely_benign	0.078	benign	-0.392	Destabilizing	None	N	0.105	neutral	N	0.4797312	None	None	I
L/W	0.3059	likely_benign	0.299	benign	-0.675	Destabilizing	0.864	D	0.236	neutral	None	None	None	None	I
L/Y	0.2993	likely_benign	0.2886	benign	-0.456	Destabilizing	0.356	N	0.298	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.