TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27992	84199;84200;84201	chr2:178562158;178562157;178562156	chr2:179426885;179426884;179426883
N2AB	26351	79276;79277;79278	chr2:178562158;178562157;178562156	chr2:179426885;179426884;179426883
N2A	25424	76495;76496;76497	chr2:178562158;178562157;178562156	chr2:179426885;179426884;179426883
N2B	18927	57004;57005;57006	chr2:178562158;178562157;178562156	chr2:179426885;179426884;179426883
Novex-1	19052	57379;57380;57381	chr2:178562158;178562157;178562156	chr2:179426885;179426884;179426883
Novex-2	19119	57580;57581;57582	chr2:178562158;178562157;178562156	chr2:179426885;179426884;179426883
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-142
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1817
• 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
A/S	None	None	0.165	N	0.48	0.146	0.303781844768	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
A/C	0.537	ambiguous	0.5188	ambiguous	-1.215	Destabilizing	0.981	D	0.6	neutral	None	None	None	None	N
A/D	0.9049	likely_pathogenic	0.9215	pathogenic	-0.932	Destabilizing	0.324	N	0.671	neutral	N	0.509027891	None	None	N
A/E	0.8265	likely_pathogenic	0.8539	pathogenic	-0.971	Destabilizing	0.388	N	0.617	neutral	None	None	None	None	N
A/F	0.7962	likely_pathogenic	0.7918	pathogenic	-1.16	Destabilizing	0.69	D	0.674	neutral	None	None	None	None	N
A/G	0.253	likely_benign	0.2582	benign	-1.178	Destabilizing	0.165	N	0.484	neutral	N	0.509027891	None	None	N
A/H	0.9175	likely_pathogenic	0.9259	pathogenic	-1.265	Destabilizing	0.981	D	0.637	neutral	None	None	None	None	N
A/I	0.4425	ambiguous	0.4125	ambiguous	-0.464	Destabilizing	0.241	N	0.618	neutral	None	None	None	None	N
A/K	0.943	likely_pathogenic	0.9485	pathogenic	-1.027	Destabilizing	0.388	N	0.617	neutral	None	None	None	None	N
A/L	0.3454	ambiguous	0.3399	benign	-0.464	Destabilizing	0.116	N	0.569	neutral	None	None	None	None	N
A/M	0.5186	ambiguous	0.5132	ambiguous	-0.526	Destabilizing	0.818	D	0.655	neutral	None	None	None	None	N
A/N	0.7902	likely_pathogenic	0.7966	pathogenic	-0.8	Destabilizing	0.818	D	0.68	prob.neutral	None	None	None	None	N
A/P	0.0684	likely_benign	0.0767	benign	-0.584	Destabilizing	None	N	0.287	neutral	N	0.281485872	None	None	N
A/Q	0.8325	likely_pathogenic	0.8497	pathogenic	-0.977	Destabilizing	0.818	D	0.688	prob.neutral	None	None	None	None	N
A/R	0.9129	likely_pathogenic	0.9241	pathogenic	-0.736	Destabilizing	0.818	D	0.69	prob.neutral	None	None	None	None	N
A/S	0.233	likely_benign	0.2404	benign	-1.218	Destabilizing	0.165	N	0.48	neutral	N	0.508507816	None	None	N
A/T	0.2608	likely_benign	0.2655	benign	-1.152	Destabilizing	0.324	N	0.489	neutral	N	0.508507816	None	None	N
A/V	0.2041	likely_benign	0.1928	benign	-0.584	Destabilizing	0.001	N	0.179	neutral	N	0.478184909	None	None	N
A/W	0.9611	likely_pathogenic	0.9649	pathogenic	-1.401	Destabilizing	0.981	D	0.668	neutral	None	None	None	None	N
A/Y	0.8681	likely_pathogenic	0.8774	pathogenic	-1.001	Destabilizing	0.818	D	0.673	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.