TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17628	53107;53108;53109	chr2:178607905;178607904;178607903	chr2:179472632;179472631;179472630
N2AB	15987	48184;48185;48186	chr2:178607905;178607904;178607903	chr2:179472632;179472631;179472630
N2A	15060	45403;45404;45405	chr2:178607905;178607904;178607903	chr2:179472632;179472631;179472630
N2B	8563	25912;25913;25914	chr2:178607905;178607904;178607903	chr2:179472632;179472631;179472630
Novex-1	8688	26287;26288;26289	chr2:178607905;178607904;178607903	chr2:179472632;179472631;179472630
Novex-2	8755	26488;26489;26490	chr2:178607905;178607904;178607903	chr2:179472632;179472631;179472630
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-16
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.4735
• 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
Q/R	rs1326205439	None	0.007	N	0.315	0.104	0.110078149338	gnomAD-4.0.0	1.59267E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86112E-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
Q/A	0.1954	likely_benign	0.1856	benign	-0.315	Destabilizing	None	N	0.201	neutral	None	None	None	None	N
Q/C	0.5228	ambiguous	0.4382	ambiguous	-0.089	Destabilizing	0.497	N	0.443	neutral	None	None	None	None	N
Q/D	0.4405	ambiguous	0.3822	ambiguous	0.006	Stabilizing	0.009	N	0.265	neutral	None	None	None	None	N
Q/E	0.0852	likely_benign	0.0798	benign	0.064	Stabilizing	None	N	0.135	neutral	N	0.397614035	None	None	N
Q/F	0.6605	likely_pathogenic	0.5925	pathogenic	-0.244	Destabilizing	0.497	N	0.548	neutral	None	None	None	None	N
Q/G	0.2517	likely_benign	0.2222	benign	-0.589	Destabilizing	0.004	N	0.351	neutral	None	None	None	None	N
Q/H	0.191	likely_benign	0.1537	benign	-0.244	Destabilizing	0.196	N	0.341	neutral	N	0.430958605	None	None	N
Q/I	0.3714	ambiguous	0.3441	ambiguous	0.346	Stabilizing	0.044	N	0.49	neutral	None	None	None	None	N
Q/K	0.0756	likely_benign	0.0697	benign	-0.032	Destabilizing	None	N	0.136	neutral	N	0.377836196	None	None	N
Q/L	0.1672	likely_benign	0.155	benign	0.346	Stabilizing	0.014	N	0.349	neutral	N	0.470823715	None	None	N
Q/M	0.3427	ambiguous	0.3123	benign	0.3	Stabilizing	0.497	N	0.342	neutral	None	None	None	None	N
Q/N	0.2522	likely_benign	0.2198	benign	-0.612	Destabilizing	0.018	N	0.269	neutral	None	None	None	None	N
Q/P	0.602	likely_pathogenic	0.6188	pathogenic	0.156	Stabilizing	0.028	N	0.34	neutral	N	0.476749609	None	None	N
Q/R	0.0896	likely_benign	0.082	benign	0.111	Stabilizing	0.007	N	0.315	neutral	N	0.411543338	None	None	N
Q/S	0.199	likely_benign	0.1896	benign	-0.639	Destabilizing	None	N	0.155	neutral	None	None	None	None	N
Q/T	0.1517	likely_benign	0.1352	benign	-0.402	Destabilizing	None	N	0.209	neutral	None	None	None	None	N
Q/V	0.2338	likely_benign	0.221	benign	0.156	Stabilizing	0.018	N	0.354	neutral	None	None	None	None	N
Q/W	0.5604	ambiguous	0.458	ambiguous	-0.201	Destabilizing	0.788	D	0.462	neutral	None	None	None	None	N
Q/Y	0.4334	ambiguous	0.3708	ambiguous	0.062	Stabilizing	0.22	N	0.481	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.