TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9150	27673;27674;27675	chr2:178712474;178712473;178712472	chr2:179577201;179577200;179577199
N2AB	8833	26722;26723;26724	chr2:178712474;178712473;178712472	chr2:179577201;179577200;179577199
N2A	7906	23941;23942;23943	chr2:178712474;178712473;178712472	chr2:179577201;179577200;179577199
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-77
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.5779
• 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/M	rs1553891488	None	0.304	N	0.276	0.037	0.300110245524	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs1553891488	None	0.304	N	0.276	0.037	0.300110245524	gnomAD-4.0.0	6.57367E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47059E-05	0	0
I/V	None	None	None	N	0.141	0.071	0.17948927462	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
I/A	0.1564	likely_benign	0.1535	benign	-0.598	Destabilizing	0.006	N	0.237	neutral	None	None	None	None	N
I/C	0.372	ambiguous	0.3452	ambiguous	-0.603	Destabilizing	0.781	D	0.294	neutral	None	None	None	None	N
I/D	0.2924	likely_benign	0.2754	benign	-0.206	Destabilizing	0.064	N	0.371	neutral	None	None	None	None	N
I/E	0.2096	likely_benign	0.1947	benign	-0.302	Destabilizing	0.033	N	0.356	neutral	None	None	None	None	N
I/F	0.0788	likely_benign	0.0787	benign	-0.626	Destabilizing	0.076	N	0.284	neutral	None	None	None	None	N
I/G	0.2916	likely_benign	0.2785	benign	-0.756	Destabilizing	None	N	0.193	neutral	None	None	None	None	N
I/H	0.1911	likely_benign	0.1857	benign	-0.038	Destabilizing	0.54	D	0.353	neutral	None	None	None	None	N
I/K	0.1295	likely_benign	0.1253	benign	-0.341	Destabilizing	0.001	N	0.217	neutral	N	0.39152593	None	None	N
I/L	0.083	likely_benign	0.079	benign	-0.307	Destabilizing	None	N	0.163	neutral	N	0.450248947	None	None	N
I/M	0.0703	likely_benign	0.0692	benign	-0.368	Destabilizing	0.304	N	0.276	neutral	N	0.478512983	None	None	N
I/N	0.0993	likely_benign	0.0958	benign	-0.134	Destabilizing	0.064	N	0.415	neutral	None	None	None	None	N
I/P	0.7436	likely_pathogenic	0.666	pathogenic	-0.371	Destabilizing	0.251	N	0.461	neutral	None	None	None	None	N
I/Q	0.1427	likely_benign	0.1374	benign	-0.366	Destabilizing	0.003	N	0.205	neutral	None	None	None	None	N
I/R	0.098	likely_benign	0.093	benign	0.229	Stabilizing	0.059	N	0.426	neutral	N	0.455212049	None	None	N
I/S	0.128	likely_benign	0.1248	benign	-0.576	Destabilizing	0.003	N	0.175	neutral	None	None	None	None	N
I/T	0.1097	likely_benign	0.1123	benign	-0.563	Destabilizing	None	N	0.171	neutral	N	0.460329867	None	None	N
I/V	0.07	likely_benign	0.0713	benign	-0.371	Destabilizing	None	N	0.141	neutral	N	0.398897406	None	None	N
I/W	0.3878	ambiguous	0.3617	ambiguous	-0.64	Destabilizing	0.931	D	0.334	neutral	None	None	None	None	N
I/Y	0.2078	likely_benign	0.2018	benign	-0.392	Destabilizing	0.251	N	0.368	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.