TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15616	47071;47072;47073	chr2:178618704;178618703;178618702	chr2:179483431;179483430;179483429
N2AB	13975	42148;42149;42150	chr2:178618704;178618703;178618702	chr2:179483431;179483430;179483429
N2A	13048	39367;39368;39369	chr2:178618704;178618703;178618702	chr2:179483431;179483430;179483429
N2B	6551	19876;19877;19878	chr2:178618704;178618703;178618702	chr2:179483431;179483430;179483429
Novex-1	6676	20251;20252;20253	chr2:178618704;178618703;178618702	chr2:179483431;179483430;179483429
Novex-2	6743	20452;20453;20454	chr2:178618704;178618703;178618702	chr2:179483431;179483430;179483429
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-108
• Domain position: 49
• Structural Position: 130
• Q(SASA): 0.2983
• 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
T/A	rs794727331	None	0.835	N	0.331	0.21	0.3691244813	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs794727331	None	0.835	N	0.331	0.21	0.3691244813	gnomAD-4.0.0	1.11655E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52678E-05	0	0
T/M	rs368057764	0.058	1.0	N	0.545	0.446	0.576013683475	gnomAD-2.1.1	2.15173E-04	None	None	None	None	N	None	4.14E-05	2.84E-05	None	0	1.45349E-03	None	7.84929E-04	None	4.01E-05	3.14E-05	1.41243E-04
T/M	rs368057764	0.058	1.0	N	0.545	0.446	0.576013683475	gnomAD-3.1.2	1.11969E-04	None	None	None	None	N	None	0	6.57E-05	0	0	1.16731E-03	None	0	0	2.95E-05	1.65632E-03	0
T/M	rs368057764	0.058	1.0	N	0.545	0.446	0.576013683475	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	2E-03	None
T/M	rs368057764	0.058	1.0	N	0.545	0.446	0.576013683475	gnomAD-4.0.0	9.67704E-05	None	None	None	None	N	None	1.33551E-05	3.34314E-05	None	0	6.04622E-04	None	4.69381E-05	0	3.13851E-05	7.25147E-04	3.20626E-04
T/R	rs368057764	None	0.998	N	0.54	0.482	0.559961094632	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/R	rs368057764	None	0.998	N	0.54	0.482	0.559961094632	gnomAD-4.0.0	6.5864E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47327E-05	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
T/A	0.0819	likely_benign	0.1085	benign	-0.691	Destabilizing	0.835	D	0.331	neutral	N	0.511265133	None	None	N
T/C	0.4262	ambiguous	0.5581	ambiguous	-0.398	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	N
T/D	0.2347	likely_benign	0.3084	benign	-0.207	Destabilizing	0.97	D	0.448	neutral	None	None	None	None	N
T/E	0.2348	likely_benign	0.336	benign	-0.236	Destabilizing	0.97	D	0.463	neutral	None	None	None	None	N
T/F	0.2407	likely_benign	0.355	ambiguous	-0.889	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
T/G	0.1648	likely_benign	0.2092	benign	-0.913	Destabilizing	0.97	D	0.495	neutral	None	None	None	None	N
T/H	0.2454	likely_benign	0.3187	benign	-1.203	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
T/I	0.2059	likely_benign	0.3291	benign	-0.202	Destabilizing	0.996	D	0.509	neutral	None	None	None	None	N
T/K	0.1729	likely_benign	0.2181	benign	-0.694	Destabilizing	0.984	D	0.449	neutral	N	0.504306026	None	None	N
T/L	0.1208	likely_benign	0.1671	benign	-0.202	Destabilizing	0.985	D	0.426	neutral	None	None	None	None	N
T/M	0.1076	likely_benign	0.1506	benign	0.129	Stabilizing	1.0	D	0.545	neutral	N	0.516275123	None	None	N
T/N	0.1047	likely_benign	0.1202	benign	-0.57	Destabilizing	0.97	D	0.414	neutral	None	None	None	None	N
T/P	0.2662	likely_benign	0.347	ambiguous	-0.333	Destabilizing	0.994	D	0.511	neutral	N	0.515493618	None	None	N
T/Q	0.2057	likely_benign	0.2702	benign	-0.783	Destabilizing	0.996	D	0.542	neutral	None	None	None	None	N
T/R	0.1677	likely_benign	0.2123	benign	-0.39	Destabilizing	0.998	D	0.54	neutral	N	0.511265133	None	None	N
T/S	0.082	likely_benign	0.0963	benign	-0.818	Destabilizing	0.287	N	0.147	neutral	N	0.49705073	None	None	N
T/V	0.1476	likely_benign	0.2264	benign	-0.333	Destabilizing	0.985	D	0.387	neutral	None	None	None	None	N
T/W	0.5973	likely_pathogenic	0.7008	pathogenic	-0.83	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/Y	0.3174	likely_benign	0.3988	ambiguous	-0.6	Destabilizing	0.999	D	0.691	prob.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.