TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7942	24049;24050;24051	chr2:178719668;178719667;178719666	chr2:179584395;179584394;179584393
N2AB	7625	23098;23099;23100	chr2:178719668;178719667;178719666	chr2:179584395;179584394;179584393
N2A	6698	20317;20318;20319	chr2:178719668;178719667;178719666	chr2:179584395;179584394;179584393
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-64
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.5832
• 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	rs780339774	0.605	0.005	D	0.196	0.115	0.260249123532	gnomAD-2.1.1	4.02E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.26797E-04	None	0	0	0
K/E	rs780339774	0.605	0.005	D	0.196	0.115	0.260249123532	gnomAD-4.0.0	2.18951E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.70989E-04	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	0.3214	likely_benign	0.4218	ambiguous	-0.486	Destabilizing	0.016	N	0.401	neutral	None	None	None	None	N
K/C	0.6494	likely_pathogenic	0.7544	pathogenic	-0.662	Destabilizing	0.864	D	0.451	neutral	None	None	None	None	N
K/D	0.3109	likely_benign	0.4038	ambiguous	0.288	Stabilizing	None	N	0.201	neutral	None	None	None	None	N
K/E	0.1591	likely_benign	0.1906	benign	0.432	Stabilizing	0.005	N	0.196	neutral	D	0.523514554	None	None	N
K/F	0.8105	likely_pathogenic	0.8666	pathogenic	-0.212	Destabilizing	0.628	D	0.473	neutral	None	None	None	None	N
K/G	0.2443	likely_benign	0.3029	benign	-0.839	Destabilizing	0.016	N	0.437	neutral	None	None	None	None	N
K/H	0.1862	likely_benign	0.2447	benign	-0.916	Destabilizing	0.214	N	0.447	neutral	None	None	None	None	N
K/I	0.6459	likely_pathogenic	0.7425	pathogenic	0.425	Stabilizing	0.295	N	0.497	neutral	D	0.531437627	None	None	N
K/L	0.4561	ambiguous	0.5624	ambiguous	0.425	Stabilizing	0.072	N	0.469	neutral	None	None	None	None	N
K/M	0.2852	likely_benign	0.344	ambiguous	0.02	Stabilizing	0.356	N	0.439	neutral	None	None	None	None	N
K/N	0.1535	likely_benign	0.2095	benign	-0.388	Destabilizing	None	N	0.143	neutral	N	0.448267434	None	None	N
K/P	0.8256	likely_pathogenic	0.8832	pathogenic	0.151	Stabilizing	0.136	N	0.477	neutral	None	None	None	None	N
K/Q	0.1182	likely_benign	0.1343	benign	-0.311	Destabilizing	0.001	N	0.149	neutral	D	0.533635547	None	None	N
K/R	0.0795	likely_benign	0.0849	benign	-0.258	Destabilizing	None	N	0.116	neutral	N	0.510452043	None	None	N
K/S	0.2464	likely_benign	0.328	benign	-1.065	Destabilizing	0.016	N	0.265	neutral	None	None	None	None	N
K/T	0.1915	likely_benign	0.2468	benign	-0.699	Destabilizing	0.012	N	0.413	neutral	N	0.501024484	None	None	N
K/V	0.5629	ambiguous	0.6641	pathogenic	0.151	Stabilizing	0.072	N	0.478	neutral	None	None	None	None	N
K/W	0.7425	likely_pathogenic	0.8145	pathogenic	-0.142	Destabilizing	0.864	D	0.479	neutral	None	None	None	None	N
K/Y	0.5073	ambiguous	0.6049	pathogenic	0.177	Stabilizing	0.356	N	0.473	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.