TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25839	77740;77741;77742	chr2:178568617;178568616;178568615	chr2:179433344;179433343;179433342
N2AB	24198	72817;72818;72819	chr2:178568617;178568616;178568615	chr2:179433344;179433343;179433342
N2A	23271	70036;70037;70038	chr2:178568617;178568616;178568615	chr2:179433344;179433343;179433342
N2B	16774	50545;50546;50547	chr2:178568617;178568616;178568615	chr2:179433344;179433343;179433342
Novex-1	16899	50920;50921;50922	chr2:178568617;178568616;178568615	chr2:179433344;179433343;179433342
Novex-2	16966	51121;51122;51123	chr2:178568617;178568616;178568615	chr2:179433344;179433343;179433342
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: Ig-136
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.9145
• 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	rs1371831965	None	0.993	N	0.631	0.384	0.358948522604	gnomAD-4.0.0	6.8435E-06	None	None	None	None	N	None	2.98972E-05	0	None	0	0	None	0	0	8.09666E-06	0	0
K/R	None	None	0.235	N	0.339	0.143	0.396044805602	gnomAD-4.0.0	2.05306E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99632E-07	0	3.31411E-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	0.7278	likely_pathogenic	0.7302	pathogenic	0.032	Stabilizing	0.983	D	0.619	neutral	None	None	None	None	N
K/C	0.8357	likely_pathogenic	0.84	pathogenic	-0.468	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/D	0.931	likely_pathogenic	0.9296	pathogenic	-0.246	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
K/E	0.5943	likely_pathogenic	0.5835	pathogenic	-0.238	Destabilizing	0.977	D	0.593	neutral	N	0.514684427	None	None	N
K/F	0.9248	likely_pathogenic	0.9256	pathogenic	-0.263	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/G	0.8136	likely_pathogenic	0.8078	pathogenic	-0.121	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	N
K/H	0.4605	ambiguous	0.463	ambiguous	-0.233	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
K/I	0.6121	likely_pathogenic	0.6187	pathogenic	0.355	Stabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
K/L	0.5617	ambiguous	0.5756	pathogenic	0.355	Stabilizing	0.995	D	0.583	neutral	None	None	None	None	N
K/M	0.529	ambiguous	0.5331	ambiguous	-0.127	Destabilizing	1.0	D	0.665	neutral	N	0.491723625	None	None	N
K/N	0.8344	likely_pathogenic	0.8325	pathogenic	-0.062	Destabilizing	0.993	D	0.644	neutral	N	0.484465015	None	None	N
K/P	0.8236	likely_pathogenic	0.8363	pathogenic	0.272	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	N
K/Q	0.2318	likely_benign	0.2323	benign	-0.151	Destabilizing	0.993	D	0.631	neutral	N	0.483592869	None	None	N
K/R	0.0842	likely_benign	0.0819	benign	-0.12	Destabilizing	0.235	N	0.339	neutral	N	0.509027891	None	None	N
K/S	0.8006	likely_pathogenic	0.8049	pathogenic	-0.4	Destabilizing	0.983	D	0.604	neutral	None	None	None	None	N
K/T	0.525	ambiguous	0.5315	ambiguous	-0.265	Destabilizing	0.997	D	0.631	neutral	N	0.513953708	None	None	N
K/V	0.5871	likely_pathogenic	0.5966	pathogenic	0.272	Stabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
K/W	0.8938	likely_pathogenic	0.8924	pathogenic	-0.39	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/Y	0.8393	likely_pathogenic	0.8415	pathogenic	-0.029	Destabilizing	0.999	D	0.675	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.