TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33556	100891;100892;100893	chr2:178536081;178536080;178536079	chr2:179400808;179400807;179400806
N2AB	31915	95968;95969;95970	chr2:178536081;178536080;178536079	chr2:179400808;179400807;179400806
N2A	30988	93187;93188;93189	chr2:178536081;178536080;178536079	chr2:179400808;179400807;179400806
N2B	24491	73696;73697;73698	chr2:178536081;178536080;178536079	chr2:179400808;179400807;179400806
Novex-1	24616	74071;74072;74073	chr2:178536081;178536080;178536079	chr2:179400808;179400807;179400806
Novex-2	24683	74272;74273;74274	chr2:178536081;178536080;178536079	chr2:179400808;179400807;179400806
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-158
• Domain position: 61
• Structural Position: 139
• Q(SASA): 0.1334
• 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
I/L	None	None	0.006	N	0.447	0.202	0.346768085243	gnomAD-4.0.0	1.68175E-05	None	None	None	None	N	None	6.34035E-05	0	None	0	0	None	0	0	1.70755E-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
I/A	0.8124	likely_pathogenic	0.7407	pathogenic	-2.384	Highly Destabilizing	0.592	D	0.466	neutral	None	None	None	None	N
I/C	0.9034	likely_pathogenic	0.8778	pathogenic	-1.71	Destabilizing	0.995	D	0.543	neutral	None	None	None	None	N
I/D	0.9728	likely_pathogenic	0.9479	pathogenic	-2.513	Highly Destabilizing	0.993	D	0.6	neutral	None	None	None	None	N
I/E	0.9304	likely_pathogenic	0.8699	pathogenic	-2.428	Highly Destabilizing	0.974	D	0.596	neutral	None	None	None	None	N
I/F	0.533	ambiguous	0.4029	ambiguous	-1.525	Destabilizing	0.881	D	0.507	neutral	N	0.472125729	None	None	N
I/G	0.9599	likely_pathogenic	0.9365	pathogenic	-2.796	Highly Destabilizing	0.934	D	0.586	neutral	None	None	None	None	N
I/H	0.8795	likely_pathogenic	0.7812	pathogenic	-2.012	Highly Destabilizing	0.996	D	0.621	neutral	None	None	None	None	N
I/K	0.9055	likely_pathogenic	0.8194	pathogenic	-1.866	Destabilizing	0.595	D	0.599	neutral	None	None	None	None	N
I/L	0.2731	likely_benign	0.2412	benign	-1.255	Destabilizing	0.006	N	0.447	neutral	N	0.449152868	None	None	N
I/M	0.2347	likely_benign	0.1998	benign	-1.121	Destabilizing	0.689	D	0.547	neutral	N	0.492405	None	None	N
I/N	0.6863	likely_pathogenic	0.5911	pathogenic	-1.861	Destabilizing	0.991	D	0.607	neutral	N	0.472645804	None	None	N
I/P	0.9974	likely_pathogenic	0.9962	pathogenic	-1.607	Destabilizing	0.993	D	0.607	neutral	None	None	None	None	N
I/Q	0.8251	likely_pathogenic	0.7039	pathogenic	-1.976	Destabilizing	0.984	D	0.612	neutral	None	None	None	None	N
I/R	0.8683	likely_pathogenic	0.757	pathogenic	-1.262	Destabilizing	0.952	D	0.607	neutral	None	None	None	None	N
I/S	0.7347	likely_pathogenic	0.6334	pathogenic	-2.487	Highly Destabilizing	0.841	D	0.541	neutral	N	0.477070188	None	None	N
I/T	0.5451	ambiguous	0.4737	ambiguous	-2.287	Highly Destabilizing	0.614	D	0.543	neutral	N	0.402839002	None	None	N
I/V	0.1042	likely_benign	0.1186	benign	-1.607	Destabilizing	None	N	0.269	neutral	N	0.401129635	None	None	N
I/W	0.9671	likely_pathogenic	0.9373	pathogenic	-1.72	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
I/Y	0.8714	likely_pathogenic	0.7778	pathogenic	-1.523	Destabilizing	0.699	D	0.545	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.