TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17715	53368;53369;53370	chr2:178607545;178607544;178607543	chr2:179472272;179472271;179472270
N2AB	16074	48445;48446;48447	chr2:178607545;178607544;178607543	chr2:179472272;179472271;179472270
N2A	15147	45664;45665;45666	chr2:178607545;178607544;178607543	chr2:179472272;179472271;179472270
N2B	8650	26173;26174;26175	chr2:178607545;178607544;178607543	chr2:179472272;179472271;179472270
Novex-1	8775	26548;26549;26550	chr2:178607545;178607544;178607543	chr2:179472272;179472271;179472270
Novex-2	8842	26749;26750;26751	chr2:178607545;178607544;178607543	chr2:179472272;179472271;179472270
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-113
• Domain position: 39
• Structural Position: 70
• Q(SASA): 0.9705
• 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
K/E	None	None	0.767	N	0.367	0.203	0.3085936734	gnomAD-4.0.0	1.59232E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41546E-04	0	0	0
K/N	rs2055193492	None	0.999	N	0.593	0.3	0.349429436713	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs2055193492	None	0.999	N	0.593	0.3	0.349429436713	gnomAD-4.0.0	6.57843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47202E-05	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
K/A	0.2293	likely_benign	0.2135	benign	0.087	Stabilizing	0.997	D	0.558	neutral	None	None	None	None	N
K/C	0.7005	likely_pathogenic	0.6902	pathogenic	-0.068	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/D	0.3854	ambiguous	0.3823	ambiguous	0.102	Stabilizing	0.994	D	0.562	neutral	None	None	None	None	N
K/E	0.1199	likely_benign	0.1181	benign	0.114	Stabilizing	0.767	D	0.367	neutral	N	0.474989888	None	None	N
K/F	0.7389	likely_pathogenic	0.7529	pathogenic	-0.092	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/G	0.2967	likely_benign	0.2908	benign	-0.123	Destabilizing	1.0	D	0.495	neutral	None	None	None	None	N
K/H	0.3419	ambiguous	0.3336	benign	-0.427	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
K/I	0.3252	likely_benign	0.3215	benign	0.564	Stabilizing	1.0	D	0.661	neutral	D	0.523189267	None	None	N
K/L	0.3265	likely_benign	0.3212	benign	0.564	Stabilizing	1.0	D	0.514	neutral	None	None	None	None	N
K/M	0.2183	likely_benign	0.212	benign	0.311	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
K/N	0.3117	likely_benign	0.3108	benign	0.343	Stabilizing	0.999	D	0.593	neutral	N	0.455617481	None	None	N
K/P	0.3514	ambiguous	0.3006	benign	0.433	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	N
K/Q	0.1452	likely_benign	0.1386	benign	0.188	Stabilizing	0.999	D	0.569	neutral	N	0.499810975	None	None	N
K/R	0.0958	likely_benign	0.0974	benign	0.004	Stabilizing	0.996	D	0.549	neutral	N	0.500677767	None	None	N
K/S	0.2904	likely_benign	0.276	benign	-0.121	Destabilizing	0.997	D	0.566	neutral	None	None	None	None	N
K/T	0.1364	likely_benign	0.1293	benign	0.04	Stabilizing	0.999	D	0.567	neutral	N	0.471605654	None	None	N
K/V	0.2855	likely_benign	0.2749	benign	0.433	Stabilizing	1.0	D	0.595	neutral	None	None	None	None	N
K/W	0.7349	likely_pathogenic	0.7397	pathogenic	-0.128	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/Y	0.6093	likely_pathogenic	0.6255	pathogenic	0.229	Stabilizing	1.0	D	0.615	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.