TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26743	80452;80453;80454	chr2:178565905;178565904;178565903	chr2:179430632;179430631;179430630
N2AB	25102	75529;75530;75531	chr2:178565905;178565904;178565903	chr2:179430632;179430631;179430630
N2A	24175	72748;72749;72750	chr2:178565905;178565904;178565903	chr2:179430632;179430631;179430630
N2B	17678	53257;53258;53259	chr2:178565905;178565904;178565903	chr2:179430632;179430631;179430630
Novex-1	17803	53632;53633;53634	chr2:178565905;178565904;178565903	chr2:179430632;179430631;179430630
Novex-2	17870	53833;53834;53835	chr2:178565905;178565904;178565903	chr2:179430632;179430631;179430630
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: Fn3-82
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.315
• 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/T	rs368263400	-0.904	0.097	N	0.489	0.135	0.170165803431	gnomAD-2.1.1	8.04E-05	None	None	None	None	N	None	0	0	None	0	2.23065E-04	None	3.92182E-04	None	0	3.56E-05	0
K/T	rs368263400	-0.904	0.097	N	0.489	0.135	0.170165803431	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	3.861E-04	None	0	0	1.47E-05	0	0
K/T	rs368263400	-0.904	0.097	N	0.489	0.135	0.170165803431	gnomAD-4.0.0	2.7269E-05	None	None	None	None	N	None	0	0	None	0	1.33767E-04	None	0	0	9.32458E-06	2.52525E-04	6.40533E-05

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	0.5325	ambiguous	0.4981	ambiguous	-0.779	Destabilizing	0.163	N	0.456	neutral	None	None	None	None	N
K/C	0.6172	likely_pathogenic	0.6356	pathogenic	-0.76	Destabilizing	0.975	D	0.637	neutral	None	None	None	None	N
K/D	0.8818	likely_pathogenic	0.8594	pathogenic	0.203	Stabilizing	0.624	D	0.561	neutral	None	None	None	None	N
K/E	0.4381	ambiguous	0.3887	ambiguous	0.348	Stabilizing	0.051	N	0.455	neutral	N	0.519980312	None	None	N
K/F	0.8266	likely_pathogenic	0.7961	pathogenic	-0.458	Destabilizing	0.397	N	0.625	neutral	None	None	None	None	N
K/G	0.7708	likely_pathogenic	0.7358	pathogenic	-1.136	Destabilizing	0.321	N	0.533	neutral	None	None	None	None	N
K/H	0.31	likely_benign	0.2979	benign	-1.18	Destabilizing	0.582	D	0.571	neutral	None	None	None	None	N
K/I	0.3708	ambiguous	0.3592	ambiguous	0.154	Stabilizing	0.018	N	0.619	neutral	N	0.470861806	None	None	N
K/L	0.3986	ambiguous	0.3704	ambiguous	0.154	Stabilizing	0.001	N	0.502	neutral	None	None	None	None	N
K/M	0.3071	likely_benign	0.2771	benign	-0.126	Destabilizing	0.005	N	0.404	neutral	None	None	None	None	N
K/N	0.7479	likely_pathogenic	0.7039	pathogenic	-0.47	Destabilizing	0.263	N	0.479	neutral	N	0.468886796	None	None	N
K/P	0.782	likely_pathogenic	0.7709	pathogenic	-0.129	Destabilizing	0.771	D	0.575	neutral	None	None	None	None	N
K/Q	0.1902	likely_benign	0.1713	benign	-0.439	Destabilizing	0.041	N	0.486	neutral	D	0.522655257	None	None	N
K/R	0.0678	likely_benign	0.0691	benign	-0.319	Destabilizing	None	N	0.168	neutral	N	0.459972003	None	None	N
K/S	0.6818	likely_pathogenic	0.632	pathogenic	-1.215	Destabilizing	0.321	N	0.433	neutral	None	None	None	None	N
K/T	0.2926	likely_benign	0.2597	benign	-0.847	Destabilizing	0.097	N	0.489	neutral	N	0.437628287	None	None	N
K/V	0.3597	ambiguous	0.3467	ambiguous	-0.129	Destabilizing	0.009	N	0.541	neutral	None	None	None	None	N
K/W	0.7325	likely_pathogenic	0.7179	pathogenic	-0.313	Destabilizing	0.983	D	0.657	neutral	None	None	None	None	N
K/Y	0.6844	likely_pathogenic	0.6736	pathogenic	-0.037	Destabilizing	0.135	N	0.616	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.