TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28809	86650;86651;86652	chr2:178559707;178559706;178559705	chr2:179424434;179424433;179424432
N2AB	27168	81727;81728;81729	chr2:178559707;178559706;178559705	chr2:179424434;179424433;179424432
N2A	26241	78946;78947;78948	chr2:178559707;178559706;178559705	chr2:179424434;179424433;179424432
N2B	19744	59455;59456;59457	chr2:178559707;178559706;178559705	chr2:179424434;179424433;179424432
Novex-1	19869	59830;59831;59832	chr2:178559707;178559706;178559705	chr2:179424434;179424433;179424432
Novex-2	19936	60031;60032;60033	chr2:178559707;178559706;178559705	chr2:179424434;179424433;179424432
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-144
• Domain position: 55
• Structural Position: 137
• Q(SASA): 0.2348
• 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	rs1702904098	None	None	N	0.209	0.118	0.216624796971	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
S/A	0.0818	likely_benign	0.0937	benign	-0.855	Destabilizing	None	N	0.231	neutral	N	0.516706012	None	None	N
S/C	0.0931	likely_benign	0.1083	benign	-0.873	Destabilizing	0.824	D	0.562	neutral	None	None	None	None	N
S/D	0.6427	likely_pathogenic	0.6737	pathogenic	-1.575	Destabilizing	0.149	N	0.52	neutral	None	None	None	None	N
S/E	0.5782	likely_pathogenic	0.6441	pathogenic	-1.427	Destabilizing	0.149	N	0.524	neutral	None	None	None	None	N
S/F	0.1761	likely_benign	0.2042	benign	-0.923	Destabilizing	0.235	N	0.625	neutral	None	None	None	None	N
S/G	0.1924	likely_benign	0.2016	benign	-1.207	Destabilizing	0.081	N	0.494	neutral	None	None	None	None	N
S/H	0.3764	ambiguous	0.4125	ambiguous	-1.665	Destabilizing	0.935	D	0.56	neutral	None	None	None	None	N
S/I	0.1471	likely_benign	0.1725	benign	0.016	Stabilizing	0.081	N	0.567	neutral	None	None	None	None	N
S/K	0.7182	likely_pathogenic	0.7775	pathogenic	-0.461	Destabilizing	0.149	N	0.521	neutral	None	None	None	None	N
S/L	0.0922	likely_benign	0.1163	benign	0.016	Stabilizing	None	N	0.42	neutral	N	0.471800442	None	None	N
S/M	0.1493	likely_benign	0.1755	benign	0.069	Stabilizing	0.235	N	0.586	neutral	None	None	None	None	N
S/N	0.2548	likely_benign	0.2548	benign	-1.103	Destabilizing	0.149	N	0.537	neutral	None	None	None	None	N
S/P	0.9738	likely_pathogenic	0.9782	pathogenic	-0.24	Destabilizing	0.484	N	0.577	neutral	N	0.515348062	None	None	N
S/Q	0.4748	ambiguous	0.5286	ambiguous	-1.0	Destabilizing	0.555	D	0.564	neutral	None	None	None	None	N
S/R	0.6502	likely_pathogenic	0.7	pathogenic	-0.691	Destabilizing	0.38	N	0.578	neutral	None	None	None	None	N
S/T	0.0748	likely_benign	0.0803	benign	-0.795	Destabilizing	None	N	0.209	neutral	N	0.441165316	None	None	N
S/V	0.1325	likely_benign	0.157	benign	-0.24	Destabilizing	0.081	N	0.531	neutral	None	None	None	None	N
S/W	0.3672	ambiguous	0.4226	ambiguous	-1.116	Destabilizing	0.935	D	0.68	prob.neutral	None	None	None	None	N
S/Y	0.1997	likely_benign	0.2282	benign	-0.687	Destabilizing	0.555	D	0.624	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.