TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34310	103153;103154;103155	chr2:178533687;178533686;178533685	chr2:179398414;179398413;179398412
N2AB	32669	98230;98231;98232	chr2:178533687;178533686;178533685	chr2:179398414;179398413;179398412
N2A	31742	95449;95450;95451	chr2:178533687;178533686;178533685	chr2:179398414;179398413;179398412
N2B	25245	75958;75959;75960	chr2:178533687;178533686;178533685	chr2:179398414;179398413;179398412
Novex-1	25370	76333;76334;76335	chr2:178533687;178533686;178533685	chr2:179398414;179398413;179398412
Novex-2	25437	76534;76535;76536	chr2:178533687;178533686;178533685	chr2:179398414;179398413;179398412
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-161
• Domain position: 53
• Structural Position: 125
• Q(SASA): 0.4447
• 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
E/K	rs768930172	-0.223	0.92	N	0.266	0.254	0.273938319068	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
E/K	rs768930172	-0.223	0.92	N	0.266	0.254	0.273938319068	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs768930172	-0.223	0.92	N	0.266	0.254	0.273938319068	gnomAD-4.0.0	2.4786E-06	None	None	None	None	N	None	4.00459E-05	0	None	0	0	None	0	0	8.4755E-07	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
E/A	0.2042	likely_benign	0.1865	benign	-0.37	Destabilizing	0.704	D	0.323	neutral	N	0.486593749	None	None	N
E/C	0.8503	likely_pathogenic	0.8291	pathogenic	0.134	Stabilizing	0.999	D	0.418	neutral	None	None	None	None	N
E/D	0.2592	likely_benign	0.2425	benign	-0.379	Destabilizing	0.826	D	0.28	neutral	N	0.461274017	None	None	N
E/F	0.7335	likely_pathogenic	0.709	pathogenic	-0.359	Destabilizing	0.991	D	0.445	neutral	None	None	None	None	N
E/G	0.3424	ambiguous	0.3103	benign	-0.583	Destabilizing	0.92	D	0.339	neutral	N	0.47784098	None	None	N
E/H	0.4575	ambiguous	0.4203	ambiguous	-0.394	Destabilizing	0.997	D	0.36	neutral	None	None	None	None	N
E/I	0.2915	likely_benign	0.2888	benign	0.159	Stabilizing	0.884	D	0.372	neutral	None	None	None	None	N
E/K	0.1992	likely_benign	0.1805	benign	0.365	Stabilizing	0.92	D	0.266	neutral	N	0.399993485	None	None	N
E/L	0.4133	ambiguous	0.399	ambiguous	0.159	Stabilizing	0.759	D	0.369	neutral	None	None	None	None	N
E/M	0.4714	ambiguous	0.467	ambiguous	0.397	Stabilizing	0.991	D	0.402	neutral	None	None	None	None	N
E/N	0.4251	ambiguous	0.3832	ambiguous	0.104	Stabilizing	0.939	D	0.292	neutral	None	None	None	None	N
E/P	0.9719	likely_pathogenic	0.9653	pathogenic	0.003	Stabilizing	0.991	D	0.359	neutral	None	None	None	None	N
E/Q	0.1426	likely_benign	0.1305	benign	0.13	Stabilizing	0.959	D	0.321	neutral	N	0.457137633	None	None	N
E/R	0.3107	likely_benign	0.2721	benign	0.421	Stabilizing	0.991	D	0.32	neutral	None	None	None	None	N
E/S	0.2531	likely_benign	0.2341	benign	-0.069	Destabilizing	0.373	N	0.123	neutral	None	None	None	None	N
E/T	0.2205	likely_benign	0.2064	benign	0.103	Stabilizing	0.079	N	0.151	neutral	None	None	None	None	N
E/V	0.2017	likely_benign	0.1994	benign	0.003	Stabilizing	0.134	N	0.248	neutral	N	0.445632561	None	None	N
E/W	0.9117	likely_pathogenic	0.8955	pathogenic	-0.243	Destabilizing	0.999	D	0.468	neutral	None	None	None	None	N
E/Y	0.668	likely_pathogenic	0.6368	pathogenic	-0.117	Destabilizing	0.997	D	0.423	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.