TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23968	72127;72128;72129	chr2:178574230;178574229;178574228	chr2:179438957;179438956;179438955
N2AB	22327	67204;67205;67206	chr2:178574230;178574229;178574228	chr2:179438957;179438956;179438955
N2A	21400	64423;64424;64425	chr2:178574230;178574229;178574228	chr2:179438957;179438956;179438955
N2B	14903	44932;44933;44934	chr2:178574230;178574229;178574228	chr2:179438957;179438956;179438955
Novex-1	15028	45307;45308;45309	chr2:178574230;178574229;178574228	chr2:179438957;179438956;179438955
Novex-2	15095	45508;45509;45510	chr2:178574230;178574229;178574228	chr2:179438957;179438956;179438955
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-62
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.5943
• 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
N/T	rs769320596	0.166	0.012	N	0.282	0.069	0.203808441222	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	0	None	1.99362E-04	0	None	0	None	0	1.79E-05	1.66113E-04
N/T	rs769320596	0.166	0.012	N	0.282	0.069	0.203808441222	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	8.64553E-04	0	None	0	0	0	0	0
N/T	rs769320596	0.166	0.012	N	0.282	0.069	0.203808441222	gnomAD-4.0.0	2.6655E-05	None	None	None	None	N	None	0	0	None	8.1114E-04	0	None	1.5623E-05	0	1.18693E-05	0	6.40594E-05
N/Y	None	None	0.093	N	0.409	0.175	0.359357374593	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

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
N/A	0.1148	likely_benign	0.1479	benign	-0.053	Destabilizing	None	N	0.188	neutral	None	None	None	None	N
N/C	0.2166	likely_benign	0.2649	benign	0.057	Stabilizing	0.864	D	0.402	neutral	None	None	None	None	N
N/D	0.0855	likely_benign	0.0981	benign	0.022	Stabilizing	None	N	0.111	neutral	N	0.391706783	None	None	N
N/E	0.2002	likely_benign	0.2495	benign	-0.043	Destabilizing	0.016	N	0.327	neutral	None	None	None	None	N
N/F	0.3616	ambiguous	0.4677	ambiguous	-0.697	Destabilizing	0.214	N	0.441	neutral	None	None	None	None	N
N/G	0.1396	likely_benign	0.1767	benign	-0.128	Destabilizing	0.016	N	0.26	neutral	None	None	None	None	N
N/H	0.0882	likely_benign	0.1054	benign	-0.14	Destabilizing	None	N	0.179	neutral	N	0.504242855	None	None	N
N/I	0.201	likely_benign	0.2631	benign	0.043	Stabilizing	0.295	N	0.451	neutral	D	0.523695407	None	None	N
N/K	0.1846	likely_benign	0.2289	benign	0.049	Stabilizing	0.029	N	0.267	neutral	N	0.474034591	None	None	N
N/L	0.1849	likely_benign	0.2277	benign	0.043	Stabilizing	0.072	N	0.353	neutral	None	None	None	None	N
N/M	0.2593	likely_benign	0.3134	benign	0.024	Stabilizing	0.864	D	0.365	neutral	None	None	None	None	N
N/P	0.4855	ambiguous	0.6082	pathogenic	0.033	Stabilizing	0.356	N	0.427	neutral	None	None	None	None	N
N/Q	0.1897	likely_benign	0.2295	benign	-0.292	Destabilizing	0.072	N	0.32	neutral	None	None	None	None	N
N/R	0.2184	likely_benign	0.2866	benign	0.122	Stabilizing	0.072	N	0.299	neutral	None	None	None	None	N
N/S	0.0619	likely_benign	0.0654	benign	-0.074	Destabilizing	None	N	0.099	neutral	N	0.398459397	None	None	N
N/T	0.0974	likely_benign	0.1103	benign	-0.037	Destabilizing	0.012	N	0.282	neutral	N	0.450504371	None	None	N
N/V	0.1724	likely_benign	0.2214	benign	0.033	Stabilizing	0.072	N	0.403	neutral	None	None	None	None	N
N/W	0.6298	likely_pathogenic	0.7243	pathogenic	-0.867	Destabilizing	0.864	D	0.457	neutral	None	None	None	None	N
N/Y	0.1396	likely_benign	0.171	benign	-0.529	Destabilizing	0.093	N	0.409	neutral	N	0.518846948	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.