TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29787	89584;89585;89586	chr2:178553646;178553645;178553644	chr2:179418373;179418372;179418371
N2AB	28146	84661;84662;84663	chr2:178553646;178553645;178553644	chr2:179418373;179418372;179418371
N2A	27219	81880;81881;81882	chr2:178553646;178553645;178553644	chr2:179418373;179418372;179418371
N2B	20722	62389;62390;62391	chr2:178553646;178553645;178553644	chr2:179418373;179418372;179418371
Novex-1	20847	62764;62765;62766	chr2:178553646;178553645;178553644	chr2:179418373;179418372;179418371
Novex-2	20914	62965;62966;62967	chr2:178553646;178553645;178553644	chr2:179418373;179418372;179418371
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: Fn3-105
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.8097
• Predicted PPI site: I

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	rs1217080477	0.071	0.027	N	0.283	0.107	0.186928172975	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	8.69E-05	None	0	0	None	0	None	0	0	0
K/E	rs1217080477	0.071	0.027	N	0.283	0.107	0.186928172975	gnomAD-4.0.0	4.77345E-06	None	None	None	None	I	None	0	6.85871E-05	None	0	0	None	0	0	0	0	0
K/N	None	None	0.001	N	0.106	0.095	0.0297737177859	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.1713	likely_benign	0.1841	benign	-0.151	Destabilizing	0.035	N	0.327	neutral	None	None	None	None	I
K/C	0.5544	ambiguous	0.6061	pathogenic	-0.664	Destabilizing	0.935	D	0.284	neutral	None	None	None	None	I
K/D	0.3569	ambiguous	0.3894	ambiguous	-0.487	Destabilizing	0.081	N	0.345	neutral	None	None	None	None	I
K/E	0.1377	likely_benign	0.1398	benign	-0.514	Destabilizing	0.027	N	0.283	neutral	N	0.444002473	None	None	I
K/F	0.6616	likely_pathogenic	0.6911	pathogenic	-0.563	Destabilizing	0.555	D	0.304	neutral	None	None	None	None	I
K/G	0.2468	likely_benign	0.2844	benign	-0.227	Destabilizing	0.067	N	0.332	neutral	None	None	None	None	I
K/H	0.2379	likely_benign	0.2663	benign	-0.284	Destabilizing	0.38	N	0.3	neutral	None	None	None	None	I
K/I	0.2781	likely_benign	0.2882	benign	-0.032	Destabilizing	0.484	N	0.36	neutral	N	0.460012075	None	None	I
K/L	0.284	likely_benign	0.2973	benign	-0.032	Destabilizing	0.149	N	0.419	neutral	None	None	None	None	I
K/M	0.2059	likely_benign	0.2149	benign	-0.32	Destabilizing	0.555	D	0.302	neutral	None	None	None	None	I
K/N	0.2715	likely_benign	0.3022	benign	-0.246	Destabilizing	0.001	N	0.106	neutral	N	0.459318642	None	None	I
K/P	0.357	ambiguous	0.3865	ambiguous	-0.053	Destabilizing	0.555	D	0.361	neutral	None	None	None	None	I
K/Q	0.116	likely_benign	0.1207	benign	-0.374	Destabilizing	None	N	0.191	neutral	N	0.441983675	None	None	I
K/R	0.07	likely_benign	0.0708	benign	-0.324	Destabilizing	None	N	0.119	neutral	N	0.472517226	None	None	I
K/S	0.2381	likely_benign	0.2599	benign	-0.569	Destabilizing	0.007	N	0.159	neutral	None	None	None	None	I
K/T	0.124	likely_benign	0.1314	benign	-0.503	Destabilizing	0.062	N	0.339	neutral	N	0.446330702	None	None	I
K/V	0.2282	likely_benign	0.242	benign	-0.053	Destabilizing	0.149	N	0.395	neutral	None	None	None	None	I
K/W	0.6186	likely_pathogenic	0.6661	pathogenic	-0.682	Destabilizing	0.935	D	0.331	neutral	None	None	None	None	I
K/Y	0.5046	ambiguous	0.5461	ambiguous	-0.358	Destabilizing	0.555	D	0.338	neutral	None	None	None	None	I

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.