TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18180	54763;54764;54765	chr2:178604149;178604148;178604147	chr2:179468876;179468875;179468874
N2AB	16539	49840;49841;49842	chr2:178604149;178604148;178604147	chr2:179468876;179468875;179468874
N2A	15612	47059;47060;47061	chr2:178604149;178604148;178604147	chr2:179468876;179468875;179468874
N2B	9115	27568;27569;27570	chr2:178604149;178604148;178604147	chr2:179468876;179468875;179468874
Novex-1	9240	27943;27944;27945	chr2:178604149;178604148;178604147	chr2:179468876;179468875;179468874
Novex-2	9307	28144;28145;28146	chr2:178604149;178604148;178604147	chr2:179468876;179468875;179468874
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: Fn3-20
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.511
• 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	0.625	N	0.401	0.128	0.240491677333	gnomAD-4.0.0	1.59444E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86421E-06	0	0
K/R	rs1283224972	0.139	0.005	N	0.073	0.077	0.241664281697	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66113E-04
K/R	rs1283224972	0.139	0.005	N	0.073	0.077	0.241664281697	gnomAD-4.0.0	3.18897E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	6.06024E-05

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	0.4104	ambiguous	0.2857	benign	-0.162	Destabilizing	0.688	D	0.401	neutral	None	None	None	None	N
K/C	0.7966	likely_pathogenic	0.6615	pathogenic	-0.2	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	N
K/D	0.8378	likely_pathogenic	0.7543	pathogenic	-0.034	Destabilizing	0.728	D	0.406	neutral	None	None	None	None	N
K/E	0.4224	ambiguous	0.2953	benign	-0.047	Destabilizing	0.625	D	0.401	neutral	N	0.474514594	None	None	N
K/F	0.9386	likely_pathogenic	0.8657	pathogenic	-0.564	Destabilizing	0.974	D	0.465	neutral	None	None	None	None	N
K/G	0.5035	ambiguous	0.3561	ambiguous	-0.343	Destabilizing	0.842	D	0.429	neutral	None	None	None	None	N
K/H	0.5614	ambiguous	0.386	ambiguous	-0.827	Destabilizing	0.037	N	0.248	neutral	None	None	None	None	N
K/I	0.7251	likely_pathogenic	0.6039	pathogenic	0.229	Stabilizing	0.966	D	0.481	neutral	N	0.476079272	None	None	N
K/L	0.6725	likely_pathogenic	0.5384	ambiguous	0.229	Stabilizing	0.842	D	0.449	neutral	None	None	None	None	N
K/M	0.5468	ambiguous	0.4143	ambiguous	0.367	Stabilizing	0.998	D	0.396	neutral	None	None	None	None	N
K/N	0.7437	likely_pathogenic	0.6217	pathogenic	0.243	Stabilizing	0.051	N	0.143	neutral	N	0.497623527	None	None	N
K/P	0.6875	likely_pathogenic	0.5929	pathogenic	0.126	Stabilizing	0.991	D	0.429	neutral	None	None	None	None	N
K/Q	0.2578	likely_benign	0.1716	benign	-0.066	Destabilizing	0.801	D	0.423	neutral	N	0.504512214	None	None	N
K/R	0.0764	likely_benign	0.0649	benign	0.025	Stabilizing	0.005	N	0.073	neutral	N	0.434748271	None	None	N
K/S	0.589	likely_pathogenic	0.4325	ambiguous	-0.292	Destabilizing	0.842	D	0.348	neutral	None	None	None	None	N
K/T	0.4192	ambiguous	0.3049	benign	-0.164	Destabilizing	0.801	D	0.398	neutral	N	0.501778553	None	None	N
K/V	0.6074	likely_pathogenic	0.4869	ambiguous	0.126	Stabilizing	0.974	D	0.423	neutral	None	None	None	None	N
K/W	0.9108	likely_pathogenic	0.813	pathogenic	-0.515	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	N
K/Y	0.8694	likely_pathogenic	0.7568	pathogenic	-0.128	Destabilizing	0.949	D	0.448	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.