TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2189	6790;6791;6792	chr2:178775146;178775145;178775144	chr2:179639873;179639872;179639871
N2AB	2189	6790;6791;6792	chr2:178775146;178775145;178775144	chr2:179639873;179639872;179639871
N2A	2189	6790;6791;6792	chr2:178775146;178775145;178775144	chr2:179639873;179639872;179639871
N2B	2143	6652;6653;6654	chr2:178775146;178775145;178775144	chr2:179639873;179639872;179639871
Novex-1	2143	6652;6653;6654	chr2:178775146;178775145;178775144	chr2:179639873;179639872;179639871
Novex-2	2143	6652;6653;6654	chr2:178775146;178775145;178775144	chr2:179639873;179639872;179639871
Novex-3	2189	6790;6791;6792	chr2:178775146;178775145;178775144	chr2:179639873;179639872;179639871

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-11
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2262
• 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
D/Y	rs1252868552	-0.573	1.0	N	0.791	0.55	0.355034743287	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
D/A	0.5344	ambiguous	0.5765	pathogenic	-0.385	Destabilizing	1.0	D	0.76	deleterious	N	0.341796872	None	None	N
D/C	0.9299	likely_pathogenic	0.9423	pathogenic	0.019	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
D/E	0.3925	ambiguous	0.4306	ambiguous	-0.567	Destabilizing	0.999	D	0.443	neutral	N	0.340350123	None	None	N
D/F	0.8949	likely_pathogenic	0.9116	pathogenic	-0.389	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
D/G	0.4459	ambiguous	0.4957	ambiguous	-0.633	Destabilizing	1.0	D	0.7	prob.neutral	N	0.319875835	None	None	N
D/H	0.7691	likely_pathogenic	0.8059	pathogenic	-0.575	Destabilizing	1.0	D	0.753	deleterious	N	0.361804171	None	None	N
D/I	0.8848	likely_pathogenic	0.9061	pathogenic	0.234	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
D/K	0.8881	likely_pathogenic	0.9138	pathogenic	-0.008	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
D/L	0.8533	likely_pathogenic	0.8759	pathogenic	0.234	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
D/M	0.908	likely_pathogenic	0.9246	pathogenic	0.55	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/N	0.2677	likely_benign	0.3092	benign	-0.258	Destabilizing	1.0	D	0.644	neutral	N	0.36664358	None	None	N
D/P	0.9894	likely_pathogenic	0.9909	pathogenic	0.051	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
D/Q	0.7883	likely_pathogenic	0.8234	pathogenic	-0.218	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
D/R	0.9192	likely_pathogenic	0.9364	pathogenic	0.072	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
D/S	0.4078	ambiguous	0.4494	ambiguous	-0.406	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
D/T	0.7393	likely_pathogenic	0.7786	pathogenic	-0.22	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
D/V	0.703	likely_pathogenic	0.7445	pathogenic	0.051	Stabilizing	1.0	D	0.806	deleterious	N	0.471031223	None	None	N
D/W	0.9819	likely_pathogenic	0.9848	pathogenic	-0.295	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/Y	0.5209	ambiguous	0.5702	pathogenic	-0.171	Destabilizing	1.0	D	0.791	deleterious	N	0.377576283	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.