TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25740	77443;77444;77445	chr2:178568914;178568913;178568912	chr2:179433641;179433640;179433639
N2AB	24099	72520;72521;72522	chr2:178568914;178568913;178568912	chr2:179433641;179433640;179433639
N2A	23172	69739;69740;69741	chr2:178568914;178568913;178568912	chr2:179433641;179433640;179433639
N2B	16675	50248;50249;50250	chr2:178568914;178568913;178568912	chr2:179433641;179433640;179433639
Novex-1	16800	50623;50624;50625	chr2:178568914;178568913;178568912	chr2:179433641;179433640;179433639
Novex-2	16867	50824;50825;50826	chr2:178568914;178568913;178568912	chr2:179433641;179433640;179433639
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: Fn3-75
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.5146
• 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/Q	None	None	0.998	N	0.679	0.422	0.28058544554	gnomAD-4.0.0	1.59226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85954E-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
K/A	0.3423	ambiguous	0.3414	ambiguous	0.016	Stabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/C	0.7725	likely_pathogenic	0.8012	pathogenic	0.019	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/D	0.6882	likely_pathogenic	0.6976	pathogenic	0.056	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
K/E	0.2695	likely_benign	0.2775	benign	0.092	Stabilizing	0.997	D	0.701	prob.neutral	N	0.516729363	None	None	N
K/F	0.8475	likely_pathogenic	0.8612	pathogenic	0.011	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/G	0.4313	ambiguous	0.4408	ambiguous	-0.244	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/H	0.4482	ambiguous	0.4644	ambiguous	-0.587	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	N
K/I	0.4008	ambiguous	0.4036	ambiguous	0.639	Stabilizing	0.992	D	0.685	prob.neutral	N	0.474535563	None	None	N
K/L	0.418	ambiguous	0.4284	ambiguous	0.639	Stabilizing	0.994	D	0.666	neutral	None	None	None	None	N
K/M	0.3471	ambiguous	0.3491	ambiguous	0.364	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	N
K/N	0.5265	ambiguous	0.5431	ambiguous	0.32	Stabilizing	1.0	D	0.69	prob.neutral	N	0.473321022	None	None	N
K/P	0.5565	ambiguous	0.5473	ambiguous	0.461	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/Q	0.169	likely_benign	0.1726	benign	0.197	Stabilizing	0.998	D	0.679	prob.neutral	N	0.482498054	None	None	N
K/R	0.086	likely_benign	0.0857	benign	-0.102	Destabilizing	0.996	D	0.616	neutral	N	0.478080735	None	None	N
K/S	0.4497	ambiguous	0.4567	ambiguous	-0.14	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
K/T	0.2547	likely_benign	0.254	benign	0.059	Stabilizing	0.999	D	0.661	neutral	N	0.521212463	None	None	N
K/V	0.3559	ambiguous	0.3609	ambiguous	0.461	Stabilizing	0.996	D	0.692	prob.neutral	None	None	None	None	N
K/W	0.8725	likely_pathogenic	0.8821	pathogenic	-0.002	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/Y	0.7657	likely_pathogenic	0.7822	pathogenic	0.323	Stabilizing	0.999	D	0.655	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.