TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2830	8713;8714;8715	chr2:178770213;178770212;178770211	chr2:179634940;179634939;179634938
N2AB	2830	8713;8714;8715	chr2:178770213;178770212;178770211	chr2:179634940;179634939;179634938
N2A	2830	8713;8714;8715	chr2:178770213;178770212;178770211	chr2:179634940;179634939;179634938
N2B	2784	8575;8576;8577	chr2:178770213;178770212;178770211	chr2:179634940;179634939;179634938
Novex-1	2784	8575;8576;8577	chr2:178770213;178770212;178770211	chr2:179634940;179634939;179634938
Novex-2	2784	8575;8576;8577	chr2:178770213;178770212;178770211	chr2:179634940;179634939;179634938
Novex-3	2830	8713;8714;8715	chr2:178770213;178770212;178770211	chr2:179634940;179634939;179634938

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-18
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.3819
• 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
K/N	rs768672643	0.434	0.884	N	0.307	0.142	0.0954503805726	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-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
K/A	0.4337	ambiguous	0.509	ambiguous	-0.051	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
K/C	0.6812	likely_pathogenic	0.7251	pathogenic	-0.155	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/D	0.3915	ambiguous	0.4551	ambiguous	0.083	Stabilizing	0.998	D	0.621	neutral	None	None	None	None	N
K/E	0.1908	likely_benign	0.2379	benign	0.108	Stabilizing	0.996	D	0.517	neutral	N	0.441465445	None	None	N
K/F	0.8859	likely_pathogenic	0.9172	pathogenic	-0.176	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
K/G	0.2629	likely_benign	0.2993	benign	-0.28	Destabilizing	0.997	D	0.573	neutral	None	None	None	None	N
K/H	0.2702	likely_benign	0.3048	benign	-0.595	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
K/I	0.7872	likely_pathogenic	0.8452	pathogenic	0.48	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/L	0.5638	ambiguous	0.6332	pathogenic	0.48	Stabilizing	1.0	D	0.555	neutral	None	None	None	None	N
K/M	0.4191	ambiguous	0.5031	ambiguous	0.218	Stabilizing	1.0	D	0.61	neutral	N	0.508408894	None	None	N
K/N	0.2338	likely_benign	0.2789	benign	0.208	Stabilizing	0.884	D	0.307	neutral	N	0.376866368	None	None	N
K/P	0.9229	likely_pathogenic	0.9397	pathogenic	0.332	Stabilizing	1.0	D	0.638	neutral	None	None	None	None	N
K/Q	0.114	likely_benign	0.1284	benign	0.075	Stabilizing	0.999	D	0.593	neutral	N	0.448540424	None	None	N
K/R	0.0852	likely_benign	0.0856	benign	-0.095	Destabilizing	0.998	D	0.504	neutral	N	0.441834315	None	None	N
K/S	0.3664	ambiguous	0.4305	ambiguous	-0.27	Destabilizing	0.997	D	0.53	neutral	None	None	None	None	N
K/T	0.3911	ambiguous	0.4834	ambiguous	-0.086	Destabilizing	0.999	D	0.62	neutral	N	0.465794469	None	None	N
K/V	0.699	likely_pathogenic	0.7732	pathogenic	0.332	Stabilizing	1.0	D	0.613	neutral	None	None	None	None	N
K/W	0.8714	likely_pathogenic	0.8966	pathogenic	-0.192	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
K/Y	0.6865	likely_pathogenic	0.7419	pathogenic	0.15	Stabilizing	1.0	D	0.611	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.