TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16803	50632;50633;50634	chr2:178611902;178611901;178611900	chr2:179476629;179476628;179476627
N2AB	15162	45709;45710;45711	chr2:178611902;178611901;178611900	chr2:179476629;179476628;179476627
N2A	14235	42928;42929;42930	chr2:178611902;178611901;178611900	chr2:179476629;179476628;179476627
N2B	7738	23437;23438;23439	chr2:178611902;178611901;178611900	chr2:179476629;179476628;179476627
Novex-1	7863	23812;23813;23814	chr2:178611902;178611901;178611900	chr2:179476629;179476628;179476627
Novex-2	7930	24013;24014;24015	chr2:178611902;178611901;178611900	chr2:179476629;179476628;179476627
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-10
• Domain position: 53
• Structural Position: 70
• Q(SASA): 1.012
• 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/N	None	None	0.993	N	0.701	0.318	0.282575091529	gnomAD-4.0.0	6.84645E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99831E-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
K/A	0.759	likely_pathogenic	0.7801	pathogenic	-0.495	Destabilizing	0.983	D	0.596	neutral	None	None	None	None	N
K/C	0.8751	likely_pathogenic	0.8629	pathogenic	-0.61	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/D	0.9116	likely_pathogenic	0.9234	pathogenic	0.349	Stabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	N
K/E	0.568	likely_pathogenic	0.5939	pathogenic	0.462	Stabilizing	0.977	D	0.611	neutral	N	0.470655594	None	None	N
K/F	0.9211	likely_pathogenic	0.9202	pathogenic	-0.226	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/G	0.8265	likely_pathogenic	0.8386	pathogenic	-0.827	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	N
K/H	0.5761	likely_pathogenic	0.5573	ambiguous	-0.921	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
K/I	0.6191	likely_pathogenic	0.6544	pathogenic	0.353	Stabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
K/L	0.6858	likely_pathogenic	0.6877	pathogenic	0.353	Stabilizing	0.995	D	0.575	neutral	None	None	None	None	N
K/M	0.5243	ambiguous	0.5486	ambiguous	0.019	Stabilizing	1.0	D	0.707	prob.neutral	D	0.524987518	None	None	N
K/N	0.7849	likely_pathogenic	0.8168	pathogenic	-0.25	Destabilizing	0.993	D	0.701	prob.neutral	N	0.469143398	None	None	N
K/P	0.9427	likely_pathogenic	0.9381	pathogenic	0.1	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/Q	0.3271	likely_benign	0.314	benign	-0.264	Destabilizing	0.993	D	0.702	prob.neutral	N	0.481364509	None	None	N
K/R	0.0953	likely_benign	0.093	benign	-0.289	Destabilizing	0.235	N	0.348	neutral	N	0.479546899	None	None	N
K/S	0.7767	likely_pathogenic	0.8102	pathogenic	-0.956	Destabilizing	0.983	D	0.621	neutral	None	None	None	None	N
K/T	0.4689	ambiguous	0.5262	ambiguous	-0.634	Destabilizing	0.993	D	0.649	neutral	N	0.475720965	None	None	N
K/V	0.5824	likely_pathogenic	0.6102	pathogenic	0.1	Stabilizing	0.998	D	0.65	neutral	None	None	None	None	N
K/W	0.9048	likely_pathogenic	0.8839	pathogenic	-0.109	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/Y	0.8418	likely_pathogenic	0.8423	pathogenic	0.181	Stabilizing	0.999	D	0.682	prob.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.