TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32319	97180;97181;97182	chr2:178542899;178542898;178542897	chr2:179407626;179407625;179407624
N2AB	30678	92257;92258;92259	chr2:178542899;178542898;178542897	chr2:179407626;179407625;179407624
N2A	29751	89476;89477;89478	chr2:178542899;178542898;178542897	chr2:179407626;179407625;179407624
N2B	23254	69985;69986;69987	chr2:178542899;178542898;178542897	chr2:179407626;179407625;179407624
Novex-1	23379	70360;70361;70362	chr2:178542899;178542898;178542897	chr2:179407626;179407625;179407624
Novex-2	23446	70561;70562;70563	chr2:178542899;178542898;178542897	chr2:179407626;179407625;179407624
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-154
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5327
• Predicted PPI site: I

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	rs1395301319	-0.505	0.338	N	0.481	0.267	0.233150807113	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
P/A	rs1395301319	-0.505	0.338	N	0.481	0.267	0.233150807113	gnomAD-4.0.0	1.59289E-06	None	None	None	None	I	None	0	2.28666E-05	None	0	0	None	0	0	0	0	0
P/L	None	None	0.782	N	0.656	0.252	0.647102547044	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	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
P/A	0.12	likely_benign	0.1203	benign	-1.151	Destabilizing	0.338	N	0.481	neutral	N	0.43000696	None	None	I
P/C	0.7662	likely_pathogenic	0.7311	pathogenic	-0.827	Destabilizing	0.973	D	0.711	prob.delet.	None	None	None	None	I
P/D	0.8655	likely_pathogenic	0.8253	pathogenic	-0.89	Destabilizing	0.826	D	0.48	neutral	None	None	None	None	I
P/E	0.6361	likely_pathogenic	0.5853	pathogenic	-0.944	Destabilizing	0.404	N	0.493	neutral	None	None	None	None	I
P/F	0.7021	likely_pathogenic	0.6502	pathogenic	-1.012	Destabilizing	0.906	D	0.697	prob.neutral	None	None	None	None	I
P/G	0.5526	ambiguous	0.5439	ambiguous	-1.392	Destabilizing	0.404	N	0.601	neutral	None	None	None	None	I
P/H	0.3883	ambiguous	0.3289	benign	-0.894	Destabilizing	0.004	N	0.437	neutral	None	None	None	None	I
P/I	0.4646	ambiguous	0.4477	ambiguous	-0.624	Destabilizing	0.826	D	0.697	prob.neutral	None	None	None	None	I
P/K	0.6123	likely_pathogenic	0.5429	ambiguous	-1.034	Destabilizing	0.704	D	0.479	neutral	None	None	None	None	I
P/L	0.1672	likely_benign	0.1443	benign	-0.624	Destabilizing	0.782	D	0.656	neutral	N	0.420368757	None	None	I
P/M	0.4251	ambiguous	0.4016	ambiguous	-0.494	Destabilizing	0.991	D	0.673	neutral	None	None	None	None	I
P/N	0.6475	likely_pathogenic	0.6106	pathogenic	-0.798	Destabilizing	0.704	D	0.595	neutral	None	None	None	None	I
P/Q	0.2816	likely_benign	0.2651	benign	-1.018	Destabilizing	0.782	D	0.517	neutral	N	0.441069316	None	None	I
P/R	0.4123	ambiguous	0.3522	ambiguous	-0.45	Destabilizing	0.782	D	0.658	neutral	N	0.407919534	None	None	I
P/S	0.2812	likely_benign	0.2546	benign	-1.241	Destabilizing	0.007	N	0.333	neutral	N	0.46032708	None	None	I
P/T	0.2113	likely_benign	0.1967	benign	-1.194	Destabilizing	0.338	N	0.488	neutral	N	0.447862002	None	None	I
P/V	0.3097	likely_benign	0.298	benign	-0.764	Destabilizing	0.826	D	0.627	neutral	None	None	None	None	I
P/W	0.8562	likely_pathogenic	0.8145	pathogenic	-1.137	Destabilizing	0.991	D	0.698	prob.neutral	None	None	None	None	I
P/Y	0.6844	likely_pathogenic	0.6333	pathogenic	-0.863	Destabilizing	0.826	D	0.697	prob.neutral	None	None	None	None	I

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.