TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9051	27376;27377;27378	chr2:178712874;178712873;178712872	chr2:179577601;179577600;179577599
N2AB	8734	26425;26426;26427	chr2:178712874;178712873;178712872	chr2:179577601;179577600;179577599
N2A	7807	23644;23645;23646	chr2:178712874;178712873;178712872	chr2:179577601;179577600;179577599
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-76
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.1638
• 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
S/R	rs1159097738	0.048	0.473	N	0.516	0.338	0.3085936734	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
S/R	rs1159097738	0.048	0.473	N	0.516	0.338	0.3085936734	gnomAD-4.0.0	1.36857E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99517E-07	1.15972E-05	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
S/A	0.0819	likely_benign	0.0872	benign	-0.571	Destabilizing	0.003	N	0.188	neutral	None	None	None	None	N
S/C	0.1188	likely_benign	0.1404	benign	-0.234	Destabilizing	0.975	D	0.547	neutral	N	0.517896184	None	None	N
S/D	0.2611	likely_benign	0.3185	benign	0.089	Stabilizing	0.704	D	0.453	neutral	None	None	None	None	N
S/E	0.3148	likely_benign	0.3882	ambiguous	0.161	Stabilizing	0.329	N	0.43	neutral	None	None	None	None	N
S/F	0.1641	likely_benign	0.1859	benign	-0.639	Destabilizing	0.981	D	0.555	neutral	None	None	None	None	N
S/G	0.0834	likely_benign	0.0922	benign	-0.878	Destabilizing	0.27	N	0.415	neutral	D	0.539065584	None	None	N
S/H	0.1444	likely_benign	0.1726	benign	-1.177	Destabilizing	0.981	D	0.556	neutral	None	None	None	None	N
S/I	0.1127	likely_benign	0.1388	benign	0.154	Stabilizing	0.642	D	0.569	neutral	N	0.485809889	None	None	N
S/K	0.217	likely_benign	0.2814	benign	-0.206	Destabilizing	0.001	N	0.192	neutral	None	None	None	None	N
S/L	0.0988	likely_benign	0.1096	benign	0.154	Stabilizing	0.495	N	0.505	neutral	None	None	None	None	N
S/M	0.1675	likely_benign	0.1908	benign	0.117	Stabilizing	0.981	D	0.555	neutral	None	None	None	None	N
S/N	0.0903	likely_benign	0.1034	benign	-0.381	Destabilizing	0.642	D	0.459	neutral	D	0.53090746	None	None	N
S/P	0.7984	likely_pathogenic	0.8519	pathogenic	-0.052	Destabilizing	0.828	D	0.537	neutral	None	None	None	None	N
S/Q	0.2265	likely_benign	0.2757	benign	-0.331	Destabilizing	0.704	D	0.495	neutral	None	None	None	None	N
S/R	0.1715	likely_benign	0.2209	benign	-0.298	Destabilizing	0.473	N	0.516	neutral	N	0.45864193	None	None	N
S/T	0.0715	likely_benign	0.0751	benign	-0.339	Destabilizing	0.01	N	0.214	neutral	N	0.436418432	None	None	N
S/V	0.1388	likely_benign	0.1657	benign	-0.052	Destabilizing	0.329	N	0.503	neutral	None	None	None	None	N
S/W	0.2577	likely_benign	0.3005	benign	-0.73	Destabilizing	0.995	D	0.611	neutral	None	None	None	None	N
S/Y	0.1285	likely_benign	0.1527	benign	-0.366	Destabilizing	0.981	D	0.55	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.