Table 4 Predictions based on the Project HOPE tool

rs1800968

C67S

Variant residue is less hydrophobic compared to wild-type residue; this polymorphism might disrupt hydrophobic associations in the core structural organization of the protein.

Wild-type is buried, and the variant might interrupt the core organization of this domain.

Location of the variant residue is near a conserved position and so this variation is likely to be deleterious.

rs55874920

T58S

Variant is smaller compared to wild-type amino acid and will lead to a loss of surface reactions.

Variant amino acid is positioned on the surface of a domain with undefined function.

This polymorphism is likely not damaging as homologous proteins exist with similar residues as the variant at this position.

rs56270143

G62W

Wild-type amino acid is smaller than the variant. As it is also positioned on the surface of the protein; variant can alter its external relations with other residues.

Variant amino acid is positioned on the surface of a domain with undefined function.

Wild-type amino acid is conserved, and based on conservation scores, this variant is likely deleterious.

rs140503947

Y35C

Wild-type amino acid is bigger, and the smaller variant will lead to possible loss of surface interactions.

Variant amino acid is positioned on the surface of a domain with undefined function.

Other residues have been noticed at this position. So, this variant might be found without being deleterious to the protein.

rs145468425

G57R

Wild-type amino acid is neutral in charge, and the variant is positive. This can cause repulsive reactions between the variant and neighboring residues.

Variant is positioned on the surface of a domain with undetermined role.

The amino acid is located near a conserved position, and this variant is likely damaging.

rs146603349

P50Q

Wild-type amino acid is smaller compared to the variant and is situated on the protein’s surface. The variant can interrupt interactions with other residues.

Proline is considered to be rigid and produces a specific backbone conformation. This variation has the potential to alter this distinct conformation.

Closely related residues as the variant are found at this location in other similar proteins, and this polymorphism is probably not damaging.

rs199581284

C44R

As the variant is charged, it can affect folding of the protein. In the interior of the protein, hydrophobic interactions are disrupted as the wild-type amino acid is hydrophobic than the variant.

The amino acid is buried, and the variant possibly alters the core organization of this domain.

This variation is likely damaging.

rs201260899

C44Y

Variant is bigger than the wild-type and might not fit in the core of the protein.

The amino acid is buried, and the variant might disrupt the core structure of the domain.

This variation is likely damaging.

rs371897938

G21R

As the variant is a charged residue, this can give rise to repulsion problems with charged ligands or other residues.

New residue is introduced in the signal peptide and may disturb recognition of this signal peptide. Glycine is flexible compared to other residues; this flexible nature might be important for the protein’s activity. Variant can destroy this function.

Other residues have been seen at this position. So, this variation might happen without being deleterious to the protein.

rs376876621

C59Y

Variant might not fit in the core as it is bigger than wild-type. Hydrophobic interactions are disturbed in the interior as the wild-type residue is more hydrophobic than the variant.

Wild-type is buried, and the variant might alter the core organization of this domain.

Only this residue type is found at this position, and this variation is likely damaging.