TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14435	43528;43529;43530	chr2:178632703;178632702;178632701	chr2:179497430;179497429;179497428
N2AB	12794	38605;38606;38607	chr2:178632703;178632702;178632701	chr2:179497430;179497429;179497428
N2A	11867	35824;35825;35826	chr2:178632703;178632702;178632701	chr2:179497430;179497429;179497428
N2B	5370	16333;16334;16335	chr2:178632703;178632702;178632701	chr2:179497430;179497429;179497428
Novex-1	5495	16708;16709;16710	chr2:178632703;178632702;178632701	chr2:179497430;179497429;179497428
Novex-2	5562	16909;16910;16911	chr2:178632703;178632702;178632701	chr2:179497430;179497429;179497428
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-95
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.614
• 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
P/A	None	None	0.37	D	0.247	0.346	0.386558576397	gnomAD-4.0.0	6.84374E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99628E-07	0	0
P/L	rs2059952331	None	0.241	D	0.315	0.484	0.491592572028	gnomAD-4.0.0	6.36857E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14397E-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
P/A	0.34	ambiguous	0.292	benign	-2.341	Highly Destabilizing	0.37	N	0.247	neutral	D	0.534508082	None	None	N
P/C	0.9475	likely_pathogenic	0.9255	pathogenic	-1.649	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
P/D	0.9839	likely_pathogenic	0.9839	pathogenic	-3.069	Highly Destabilizing	0.998	D	0.516	neutral	None	None	None	None	N
P/E	0.9508	likely_pathogenic	0.9463	pathogenic	-2.873	Highly Destabilizing	0.998	D	0.503	neutral	None	None	None	None	N
P/F	0.9828	likely_pathogenic	0.9772	pathogenic	-1.462	Destabilizing	0.995	D	0.664	neutral	None	None	None	None	N
P/G	0.8975	likely_pathogenic	0.8851	pathogenic	-2.845	Highly Destabilizing	0.967	D	0.51	neutral	None	None	None	None	N
P/H	0.9516	likely_pathogenic	0.9471	pathogenic	-2.557	Highly Destabilizing	1.0	D	0.567	neutral	D	0.65848691	None	None	N
P/I	0.8339	likely_pathogenic	0.7703	pathogenic	-0.924	Destabilizing	0.99	D	0.615	neutral	None	None	None	None	N
P/K	0.9763	likely_pathogenic	0.9748	pathogenic	-2.045	Highly Destabilizing	0.995	D	0.497	neutral	None	None	None	None	N
P/L	0.6232	likely_pathogenic	0.5711	pathogenic	-0.924	Destabilizing	0.241	N	0.315	neutral	D	0.65848691	None	None	N
P/M	0.8961	likely_pathogenic	0.8723	pathogenic	-0.764	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
P/N	0.9666	likely_pathogenic	0.9641	pathogenic	-2.259	Highly Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
P/Q	0.9195	likely_pathogenic	0.9133	pathogenic	-2.17	Highly Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
P/R	0.9438	likely_pathogenic	0.9413	pathogenic	-1.736	Destabilizing	0.997	D	0.581	neutral	D	0.64210868	None	None	N
P/S	0.7875	likely_pathogenic	0.7535	pathogenic	-2.815	Highly Destabilizing	0.956	D	0.499	neutral	D	0.575509291	None	None	N
P/T	0.6414	likely_pathogenic	0.6041	pathogenic	-2.495	Highly Destabilizing	0.994	D	0.473	neutral	D	0.577450217	None	None	N
P/V	0.6913	likely_pathogenic	0.6076	pathogenic	-1.373	Destabilizing	0.967	D	0.509	neutral	None	None	None	None	N
P/W	0.9946	likely_pathogenic	0.993	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
P/Y	0.9845	likely_pathogenic	0.9817	pathogenic	-1.669	Destabilizing	0.999	D	0.657	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.