TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23668	71227;71228;71229	chr2:178575130;178575129;178575128	chr2:179439857;179439856;179439855
N2AB	22027	66304;66305;66306	chr2:178575130;178575129;178575128	chr2:179439857;179439856;179439855
N2A	21100	63523;63524;63525	chr2:178575130;178575129;178575128	chr2:179439857;179439856;179439855
N2B	14603	44032;44033;44034	chr2:178575130;178575129;178575128	chr2:179439857;179439856;179439855
Novex-1	14728	44407;44408;44409	chr2:178575130;178575129;178575128	chr2:179439857;179439856;179439855
Novex-2	14795	44608;44609;44610	chr2:178575130;178575129;178575128	chr2:179439857;179439856;179439855
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-130
• Domain position: 32
• Structural Position: 49
• Q(SASA): 0.2808
• 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/R	rs1453168470	None	0.998	N	0.543	0.264	0.151104730317	gnomAD-4.0.0	8.21486E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.07968E-05	0	0
K/T	rs1453168470	-1.289	0.999	N	0.719	0.482	0.232513804876	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
K/T	rs1453168470	-1.289	0.999	N	0.719	0.482	0.232513804876	gnomAD-4.0.0	6.84571E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16031E-05	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	0.4253	ambiguous	0.4995	ambiguous	-0.928	Destabilizing	0.996	D	0.56	neutral	None	None	None	None	N
K/C	0.5341	ambiguous	0.5918	pathogenic	-1.113	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/D	0.7689	likely_pathogenic	0.8186	pathogenic	-0.754	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
K/E	0.2074	likely_benign	0.238	benign	-0.56	Destabilizing	0.998	D	0.525	neutral	N	0.475332952	None	None	N
K/F	0.6578	likely_pathogenic	0.7153	pathogenic	-0.344	Destabilizing	0.46	N	0.563	neutral	None	None	None	None	N
K/G	0.4909	ambiguous	0.5671	pathogenic	-1.367	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/H	0.2571	likely_benign	0.2903	benign	-1.615	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/I	0.3526	ambiguous	0.3795	ambiguous	0.259	Stabilizing	0.997	D	0.76	deleterious	N	0.478410543	None	None	N
K/L	0.2794	likely_benign	0.3218	benign	0.259	Stabilizing	0.983	D	0.624	neutral	None	None	None	None	N
K/M	0.1713	likely_benign	0.1876	benign	0.009	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/N	0.4898	ambiguous	0.5467	ambiguous	-1.107	Destabilizing	0.999	D	0.723	prob.delet.	N	0.511235037	None	None	N
K/P	0.9607	likely_pathogenic	0.9698	pathogenic	-0.109	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/Q	0.096	likely_benign	0.107	benign	-1.02	Destabilizing	0.999	D	0.732	prob.delet.	N	0.445703479	None	None	N
K/R	0.071	likely_benign	0.0729	benign	-0.944	Destabilizing	0.998	D	0.543	neutral	N	0.451282657	None	None	N
K/S	0.4318	ambiguous	0.506	ambiguous	-1.762	Destabilizing	0.999	D	0.576	neutral	None	None	None	None	N
K/T	0.1981	likely_benign	0.2266	benign	-1.331	Destabilizing	0.999	D	0.719	prob.delet.	N	0.403278066	None	None	N
K/V	0.3178	likely_benign	0.3488	ambiguous	-0.109	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
K/W	0.6493	likely_pathogenic	0.6934	pathogenic	-0.264	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/Y	0.5111	ambiguous	0.5637	ambiguous	0.06	Stabilizing	0.995	D	0.755	deleterious	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.