TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7880	23863;23864;23865	chr2:178720004;178720003;178720002	chr2:179584731;179584730;179584729
N2AB	7563	22912;22913;22914	chr2:178720004;178720003;178720002	chr2:179584731;179584730;179584729
N2A	6636	20131;20132;20133	chr2:178720004;178720003;178720002	chr2:179584731;179584730;179584729
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-63
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.3079
• 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
S/T	rs1158110251	-0.408	0.625	N	0.52	0.184	0.225215365344	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
S/T	rs1158110251	-0.408	0.625	N	0.52	0.184	0.225215365344	gnomAD-4.0.0	3.19568E-06	None	None	None	None	N	None	0	0	None	0	5.56204E-05	None	0	0	0	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
S/A	0.0882	likely_benign	0.0919	benign	-0.603	Destabilizing	0.005	N	0.189	neutral	D	0.528403086	None	None	N
S/C	0.1747	likely_benign	0.1687	benign	-0.428	Destabilizing	0.991	D	0.602	neutral	N	0.518639745	None	None	N
S/D	0.4768	ambiguous	0.5445	ambiguous	-0.109	Destabilizing	0.915	D	0.571	neutral	None	None	None	None	N
S/E	0.5345	ambiguous	0.597	pathogenic	-0.138	Destabilizing	0.842	D	0.55	neutral	None	None	None	None	N
S/F	0.1213	likely_benign	0.1172	benign	-0.812	Destabilizing	0.005	N	0.44	neutral	N	0.483806947	None	None	N
S/G	0.1339	likely_benign	0.14	benign	-0.829	Destabilizing	0.525	D	0.525	neutral	None	None	None	None	N
S/H	0.344	ambiguous	0.3679	ambiguous	-1.305	Destabilizing	0.991	D	0.605	neutral	None	None	None	None	N
S/I	0.1709	likely_benign	0.1696	benign	-0.119	Destabilizing	0.728	D	0.653	neutral	None	None	None	None	N
S/K	0.73	likely_pathogenic	0.7793	pathogenic	-0.729	Destabilizing	0.842	D	0.536	neutral	None	None	None	None	N
S/L	0.1008	likely_benign	0.0999	benign	-0.119	Destabilizing	0.007	N	0.453	neutral	None	None	None	None	N
S/M	0.2029	likely_benign	0.1848	benign	0.129	Stabilizing	0.949	D	0.617	neutral	None	None	None	None	N
S/N	0.1589	likely_benign	0.172	benign	-0.569	Destabilizing	0.915	D	0.588	neutral	None	None	None	None	N
S/P	0.4819	ambiguous	0.5406	ambiguous	-0.247	Destabilizing	0.966	D	0.629	neutral	N	0.503155609	None	None	N
S/Q	0.5288	ambiguous	0.5615	ambiguous	-0.754	Destabilizing	0.974	D	0.584	neutral	None	None	None	None	N
S/R	0.6014	likely_pathogenic	0.6761	pathogenic	-0.577	Destabilizing	0.974	D	0.63	neutral	None	None	None	None	N
S/T	0.0909	likely_benign	0.0911	benign	-0.622	Destabilizing	0.625	D	0.52	neutral	N	0.472048371	None	None	N
S/V	0.1723	likely_benign	0.169	benign	-0.247	Destabilizing	0.525	D	0.603	neutral	None	None	None	None	N
S/W	0.2842	likely_benign	0.2988	benign	-0.782	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
S/Y	0.1461	likely_benign	0.1472	benign	-0.532	Destabilizing	0.669	D	0.699	prob.neutral	N	0.488925695	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.