TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30673	92242;92243;92244	chr2:178549705;178549704;178549703	chr2:179414432;179414431;179414430
N2AB	29032	87319;87320;87321	chr2:178549705;178549704;178549703	chr2:179414432;179414431;179414430
N2A	28105	84538;84539;84540	chr2:178549705;178549704;178549703	chr2:179414432;179414431;179414430
N2B	21608	65047;65048;65049	chr2:178549705;178549704;178549703	chr2:179414432;179414431;179414430
Novex-1	21733	65422;65423;65424	chr2:178549705;178549704;178549703	chr2:179414432;179414431;179414430
Novex-2	21800	65623;65624;65625	chr2:178549705;178549704;178549703	chr2:179414432;179414431;179414430
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: Fn3-111
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.7235
• 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	0.027	N	0.283	0.078	0.144782658237	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/N	rs779897504	None	None	N	0.125	0.117	0.0138822411134	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	5.77812E-04	None	0	0	0	0	0
K/N	rs779897504	None	None	N	0.125	0.117	0.0138822411134	gnomAD-4.0.0	9.91552E-06	None	None	None	None	N	None	0	0	None	0	3.56665E-04	None	0	0	0	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	0.1703	likely_benign	0.1677	benign	-0.018	Destabilizing	0.002	N	0.153	neutral	None	None	None	None	N
K/C	0.3114	likely_benign	0.2632	benign	0.067	Stabilizing	0.935	D	0.242	neutral	None	None	None	None	N
K/D	0.2408	likely_benign	0.2423	benign	-0.058	Destabilizing	0.081	N	0.331	neutral	None	None	None	None	N
K/E	0.1108	likely_benign	0.1206	benign	-0.027	Destabilizing	0.027	N	0.283	neutral	N	0.412218128	None	None	N
K/F	0.4566	ambiguous	0.4379	ambiguous	-0.002	Destabilizing	0.38	N	0.271	neutral	None	None	None	None	N
K/G	0.2394	likely_benign	0.218	benign	-0.284	Destabilizing	0.035	N	0.304	neutral	None	None	None	None	N
K/H	0.1087	likely_benign	0.1041	benign	-0.656	Destabilizing	0.001	N	0.157	neutral	None	None	None	None	N
K/I	0.2107	likely_benign	0.1965	benign	0.624	Stabilizing	0.484	N	0.291	neutral	N	0.506611157	None	None	N
K/L	0.2354	likely_benign	0.2212	benign	0.624	Stabilizing	0.149	N	0.325	neutral	None	None	None	None	N
K/M	0.1611	likely_benign	0.1537	benign	0.429	Stabilizing	0.791	D	0.268	neutral	None	None	None	None	N
K/N	0.1188	likely_benign	0.1399	benign	0.274	Stabilizing	None	N	0.125	neutral	N	0.404369436	None	None	N
K/P	0.6911	likely_pathogenic	0.7248	pathogenic	0.439	Stabilizing	0.555	D	0.327	neutral	None	None	None	None	N
K/Q	0.0889	likely_benign	0.0851	benign	0.124	Stabilizing	0.117	N	0.309	neutral	N	0.49235378	None	None	N
K/R	0.0713	likely_benign	0.0701	benign	-0.155	Destabilizing	0.117	N	0.275	neutral	N	0.473594661	None	None	N
K/S	0.1497	likely_benign	0.1508	benign	-0.171	Destabilizing	0.035	N	0.257	neutral	None	None	None	None	N
K/T	0.0866	likely_benign	0.0884	benign	0.017	Stabilizing	0.062	N	0.328	neutral	N	0.454680826	None	None	N
K/V	0.1872	likely_benign	0.1678	benign	0.439	Stabilizing	0.149	N	0.347	neutral	None	None	None	None	N
K/W	0.5512	ambiguous	0.5115	ambiguous	-0.001	Destabilizing	0.935	D	0.297	neutral	None	None	None	None	N
K/Y	0.2926	likely_benign	0.2714	benign	0.308	Stabilizing	0.235	N	0.287	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.